prospect of stem cell conditioned medium in regenerative ......endothelialgrowth,homing,and aa [6]...

Review ArticleProspect of Stem Cell Conditioned Medium inRegenerative Medicine

Jeanne Adiwinata Pawitan

Department of Histology Faculty of Medicine University of Indonesia Jalan Salemba 6 Jakarta 10430 Indonesia

Correspondence should be addressed to Jeanne Adiwinata Pawitan jeanneadiwipfkuiacid

Received 11 May 2014 Revised 22 July 2014 Accepted 25 July 2014 Published 28 August 2014

Academic Editor Antonio Salgado

Copyright copy 2014 Jeanne Adiwinata Pawitan This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Background Stem cell-derived conditioned medium has a promising prospect to be produced as pharmaceuticals for regenerativemedicine Objective To investigate various methods to obtain stem cell-derived conditioned medium (CM) to get an insight intotheir prospect of application in various diseasesMethods Systematic review using keywords ldquostem cellrdquo and ldquoconditionedmediumrdquoor ldquosecretomerdquo and ldquotherapyrdquo Data concerning treated conditionsdiseases type of cell that was cultured medium and supplementsto culture the cells culture condition CMprocessing growth factors and other secretions thatwere analyzedmethod of applicationand outcome were noted grouped tabulated and analyzed ResultsMost of CM using studies showed good results However thevarious CM even when they were derived from the same kind of cells were produced by different condition that is from differentpassage culturemedium and culture conditionThe growth factor yields of the various types of cells were available in some studiesand the cell number that was needed to produce CM for one application could be computed ConclusionVarious stem cell-derivedconditionedmedia were tested on various diseases andmostly showed good results However standardized methods of productionand validations of their use need to be conducted

1 Introduction

Data of the use of stem cells in various diseases are accu-mulating Some studies reported beneficial effects of stemcell therapy in degenerative diseases such as myocardialinfarction and revealed that stem cells cause tissue repair dueto their ability to secrete trophic factors that exert beneficialimpact on the damaged tissue rather than their capacity todifferentiate into the needed cells [1] Various studies on stemcell-derived secreted factors showed that the secreted factoralone without the stem cell itself may cause tissue repair invarious conditions that involved tissueorgan damage Thesecreted factors are referred to as secretome microvesiclesor exosome and can be found in the medium where the stemcells are cultured thus the medium is called conditionedmedium (CM) [2]

The use of secretome containing CM has several advan-tages compared to the use of stem cells as CM can bemanufactured freeze-dried packaged and transportedmoreeasily Moreover as it is devoid of cells there is no needto match the donor and the recipient to avoid rejection

problems Therefore stem cell-derived conditioned mediumhave a promising prospect to be produced as pharmaceuticalsfor regenerative medicine

To date no clinical trial that used CM for a certaindisease has been reported except two pilot studies on theuse of adipose derived mesenchymal stem cell CM forhair follicle regeneration [3] and fractional carbon dioxideresurfacing wound healing [4] in human which showedgood results The use of CM for therapy is very appealingand may be booming in the near future as studies on theuse of CM for various diseases are accumulating [1 3ndash33]Conditioned medium contains various growth factors andtissue regenerative agents which were secreted by the stemcells The fact that stem cells secrete various growth factorswas also shown by various proteomic studies which revealedthe presence of various growth factors and other cytokines inthe CM [5 7ndash9 13 17 20 22 28 34 35]

However various studies reported the use of variouskinds of stem cells and various methods to get the CM tocure various kinds of degenerative diseases in various animalmodelsTherefore this systematic review aimed to investigate

Hindawi Publishing CorporationBioMed Research InternationalVolume 2014 Article ID 965849 14 pageshttpdxdoiorg1011552014965849

2 BioMed Research International

the various methods to get the CM and the various diseasesthat were treated to get an insight into the various kinds ofCM and their application benefit in various diseases

2 Materials and Methods

We performed ldquoall textrdquo searches without time restrictionon January 23 2014 in PubmedMedline using keywordsldquostem cellrdquo and ldquoconditioned mediumrdquo or ldquosecretomerdquo andldquotherapyrdquo ldquoall textrdquo searches in Cochrane library (trials) usingkeywords ldquosecretomerdquo or ldquoconditioned mediumrdquo and ldquoalltextrdquo searches in ClinicalTrialsgov using keywords ldquostemcellrdquo and ldquoconditionedmediumrdquo or ldquosecretomerdquo and ldquotherapyrdquoIn addition relevant existing articles in our library wereadded

Inclusion criteria are all studies that usedCM for a certaindisease Exclusion criteria are studies that did not containcomplete data concerning subject conditiondisease modelsource of CM and outcome of treatment with CM

Data collection is as follows treated conditionsdiseasestype of cell that was cultured detailed composition ofmedium and supplements that was used to culture the cellsculture condition (hypoxia or normoxia) to get the CM CMprocessing growth factors and other secretions that wereanalyzed method (mode) of application and outcome of CMapplication were noted grouped and tabulated

Data synthesis is as follows data were grouped accordingto treated disease and cell types that were used to producethe CM Further to know the growth factor yields of thevarious types of cells when available growth factor levelswere tabulated and grouped according to types of cells thatyielded the growth factor containing conditionedmedium inrelation to the number of cells type and duration of cultureand processing of the conditioned medium When the datawas available the number of cells thatwere needed to producethe CM for one application was computed

3 Results and Discussion

We got 39 articles that met the inclusion criteria and 7 wereexcluded due to incomplete data Various conditionsdiseaseswere treated by various cell-derived CM and mostly showedpromising results (Table 1)

The various conditioned media even when they werederived from same kind of cells were produced by differentcondition that is from different passage number of cellsculture medium and culture condition (Table 2)The growthfactor yields of the various types of cells can be seen inTable 3and the cell number that is needed to produce CM for oneapplication can be seen in Table 4

Various studies showed that conditioned medium havebeen tested in various kinds of diseasesconditions (Table 1)[1 3ndash33] that is alopecia [3 5] acute and chronic hind limbischemia [6ndash9] acute and chronic wound healing [4 10ndash14] myocardial infarct [1 15ndash18] acute liver injuryfailure[19ndash22] cerebral injuryischemiastroke [23ndash27] spinal cordinjury [28] lung injury [32] and bone defect [33] and

showed improvement of the conditions Moreover chronickidney disease that was treated using human embryonicstem cell-derived mesenchymal stem cell (huESC-MSC) CMshowed decreased systolic blood pressure and proteinuriaand improvement in tubular and glomerular damage renalblood flow and glomerular filtration rate [29] Howevernephropathy that was treated using CM from human umbili-cal cord blood unrestricted somatic stem cell (huUCB-USSC)or mouse bonemarrowmesenchymal stem cell (mBM-MSC)CM did not show improvement in serum urea and creati-nine level histopathological damage and physical activityscore [30] Moreover prevention of cancer using humanmesenchymal stem cell line CM showed increased tumor cellproliferation and vascularization [31]

In the two cases of kidney disease it can be concludedthat CM from hu-ESC-MSC can improve the condition andthe needed growth factor level is presumably enough asCM processing includes a 25-time concentration step [29]However for hu-UCB-USSC ormBM-MSC-CM lack of dataconcerning CMprocessing and growth factor level of the CM[30] prevent further analysis to conclude whether the failureto improve the condition is due to the lack of certain growthfactor or due to the level of growth factors that was too low togive an effect

The conditioned medium can be harvested from variouskinds of cells (Table 2) Moreover there are various methodsto get the conditioned medium which may interfere withthe growth factor types and levels that were harvested bythe methods Only some of the various studies using CMchecked the growth factor levels (Table 3) [5ndash10 13 17 2022 24 25 27 28 33 36] and the same type of cells yieldeddifferent growth factor levels when cell number culturemedium and condition and CM processing were different[6 24] Moreover growth factor measures also differed thatis pgmL or ngmL [6 8 10 13 17 24 27 28 33] pg120583g DNA[9 36] fgcell [25] spot density [5] and positivenegative[20] (Table 3) The measure of pg120583g DNA and fgcell can becomputed into pg or ngmL provided the DNA contentcelland cell number is known However in some studies theexact cell number that was used to produce the CM wasnot mentioned [7 8 10 13 28 33 36] In addition moststudies measured different sets of growth factors and othercytokinesfactors (Table 3)

31 Culture Medium and Supplement Some studies usedfetal bovine serum or other supplement containing completemedium while other studies used serum-free media More-over the basalmedia usedwere variable for example120572MEMDMEM DMEMF12 M199 EBM2 EGM-2 in vivo 15or chemically defined medium and the same type of cellmight be cultured in different kind of basalmedium (Table 2)Culture medium in in vitro culture represents microenvi-ronment in in vivo condition and may determine cell fateand thus cell secretion [37] Therefore the same type ofcells may secrete different level of growth factors when theywere cultured in different medium as can be seen in Table 3[25 27]

BioMed Research International 3

Table 1 Studies on various subjects conditions source of conditioned medium and outcome

Conditiondisease Subject Source of conditionedmedium Outcome Reference

numberAlopeciamdashID Human Hu-AD-MSC Increased hair growth [3]BaldmdashSC C3HHeN nude mice Hu-AD-SC Hair growth [5]

Acute hind limbischemiamdashdirect IM

Female athymic mouse Hu-AD-SC

Decreased LL and FIncreased BF angiogenesisendothelial growth homing andAA

[6]

SCID mice Hu-ESCmdashendothelialcells

Vascularization and BF CMrestored defective diabetic PBderived PAC

[7]

Chronic hind limbischemiamdash7ndash10 days IM

Male nude athymic Hu-PB-MNC-EPCHu-UC-HUVEC Increased hind limb BF [8]

Male NOD-SCID mouse Hu-AFmdashSCmdashCkit (+)

Increased arteriogenesiscapillary density total perfusionarea and mobility and decreasedmuscular deg

[9]

Skin wound directmdashID[11] SC [10 12]topicalapplication [4 13]

Human Hu-AD-SC Enhanced wound healingReduced adverse effects [4]

BALBc nude mice

(i) Hu-UCB-MNC 997888rarrUCB-SC(endothelial + MSC)(ii) HUVEC

Faster wound healingUCB-SC was better thanHUVEC

[10]

Diabeticimmunodeficient mice Hu-UCB-CD34-EPC

Faster wound closureLess granulation tissue areaMore neovascularization

[11]

Male dbdb (diabetic)mice Hu-UC-MSC Faster wound closure

Increased capillary density [12]

BALBc-nude mouse(i) Hu-ESCmdashderivedEPC(ii) Hu-UCB-EPC

Faster wound healinggranulation and reepithelizationhuESC-EPC was better thanUCB-EPC

[13]

Skin woundmdash48 hourafter woundmdashSC Male NOD-SCID mice Hu-BM-MSC Faster wound healing [14]

MCImdashdirectmdashperi-infarctinjection

Male SCID or C57BL6mouse Hu-AD-SC

Improved cardiac functionReduced infarct sizeEffect of huAD-SC gt CM

[1]

MCImdashend of 2nd hourRmdashIC Female L pig Porcine PB-EPC

Reduced IZ-A and infarct sizeIncreased IZ angiogenesisIZ cardiomyocyte hypertrophyImproved LV contractility andrelaxation

[15]

MCImdash4 hoursmdashIV(jugular vein) DL pig Hu-ESC-MSC

Increased capillary densityReduced infarct sizePreserved S-D performance

[16]

MCImdash48 hours-IM yo Rat nude athymic Hu-BM-derived MPC

Improved LV functionReduced LV dilation myocyte Aand fibrosisIncreased neovascularization

[17]

MCImdash5min beforeRmdashIV -at RmdashIC Female DL pig Hu-ESC derived MSC (i) Reduced infarct size and A

(ii) Improved S-D performance [18]

MCImdash5min beforeRmdashIVmdash(tail) Mouse Hu-ESC derived MSC

Reduced infarct size(gt1000 kD100ndash220 nm) =10ndash220 nm lt 10ndash100 nm

RSLTmdashdirectmdashIVmdash(penile) Male SD rat Rat BM-MSC Reduced LIB and PIC

Increased survival [19]


Table 1 Continued


numberAcute hepaticfailuremdash24hoursmdashintrahepatic (leftliver lobe)

CCl4 injuredSCIDNODmice

1-Hu-AF MSC2-AF-MSC-hepaticprogenitor-like cells(HPL)

(i) AST ALT decreased(ii) Liver phenotypeimprovementHPL was better than MSC-CM

[20]

Fulminant hepaticfailuremdash24 hoursmdashIV(penile)

Male SD rat Hu-MSC

Reduced ALT AST TNF120572 IL6and IL1-rec-A level and HP ICIand AIncreased IL10 level liverregeneration and survival

[21]

Male SD rat Hu-BM-MSC

Reduced panlobular leucocyteinfiltrate hepatocellular deathand bile duct duplication andincreased survival

[22]

Focal cerebralischemiamdash72hoursmdashintranasal

Male SD rat (i) Hu-SC-EDT(ii) BM-MSC (Lonza)

Increasedmigration-diffmdashendogenousNPC vasculogenesis and motorfunction and reduced infarct size(Hu SC-EDT = BM-MSC)

[23]

Ischemic strokemdashafter 8daysmdashlateral ventricleinfusion

Male SD mice Hu-AD-MSC

Motor function maintainedreduced infarct volume neuralcell A and astrogliosis andincreased microvessel

[24]

Cerebral ischemiainfarctionmdash1daymdashICintracardiac(LV) injection

immunodeficient mice

(i) Hu-BM-MSC(ii) Hu-BM-CD133(iii) Hu-BM-p75(iv) Hu-fibro

Reduced cortical infarct volume(huBM-CD133-CM lthuBM-MSC-CM lt hufibroCM lthuBM-p75CM)

[25]

Fluidpercussion-TBImdashdirectIV jugular vein


Reduced neuron loss A neuronA infarction volume and motordeficitIncreased VEGF(+) cells

[26]

Fluid percussionTBImdash12 hours aftermdashIV Male SD rat Hu-BM-MSC

Decreased brain damage volumebrain damage incidence andneuron A (hypoxia lt normoxia)Increased motorcognitivefunction and neurogenesis(hypoxia gt normoxia)

[27]

Contusion spinal cordinjurymdashdirect Female Wistar rat Rat-BM-MSC Increased motor recovery [28]

Chronic kidneydiseasemdashweek 5mdashIV(tail)

Male Le ratHu embryonicMSCmdashstablemdash80population doublings

Decreased systolic BPproteinuria and tubular +glomerular damageIncreased inulin and PAHclearance glomerularendothelium and DNA repair

[29]

Nephropathymdash24 hoursmdashIV (tail) Mouse BALBc (i) Hu-UCB-USSC

(ii) Mouse BM-MSC

No improvement in serum ureaand creatinine HP and physicalactivity score

[30]

Normalmdashcancer cell line+ CM xenograft BALB mice Hu-MSC (cell line)

Increased tumor cellproliferation (PCNA) andvascularization

[31]

VILImdashbeforeinductionmdashIVmdash(tail) Male C57BL6 mouse Mouse-iPSC

Reduced tidal volume andbronchial microstructurerestored

[32]


Table 1 Continued


numberIntrabony periodontaldefect directmdashimplant Hybrid dog Hu-MSC (Lonza) Increased alveolar bone and

cementum regeneration [33]

ID intradermal IM intramuscular SC subcutaneous MCI myocardial infarct R reperfusion IC intracoronary artery IV intravenous Imyointramyocardial LV left ventricular RSLT 50 reduced size liver transplantation TBI traumatic brain injury VILI ventilator induced lung injury SCIDsevere combined immunodeficient NOD nonobese diabetic SD Sprague-Dawley DL Dalland Landrace L Landrace W Wistar Le Lewis hu humanAD adipose tissue derived MSC mesenchymal stem cells SC stem cell ESC embryonic stem cell PB peripheral blood MNC mononuclear cell UCumbilical cord UCB UC blood BM bonemarrow EPC endothelial progenitor cell HUVEC human umbilical vein endothelial cell AF amniotic fluid EDTexfoliated deciduous tooth MPC mesenchymal progenitor cell USSC unrestricted somatic stem cell iPSC induced pluripotent stem cell LL limb lost Ffibrosis BF blood flow AA antiapoptosis CM conditioned medium PAC proangiogenic cells deg degeneration IZ infarct zone A apoptosis ALT alanineamino transferase AST aspartate aminotransferase HP histopathology ICI immune cell infiltration S-D systolic-diastolic LIB liver injury biomarker PICproinflammatory cytokine Hu-SC- IL1-rec-A IL1 receptor antagonist NPC neural progenitor cell PAH para amino hippuric acid

32 Culture Duration Production of CM varies in cultureduration from sixteen hours to five days (Table 3) In casecomplete medium was used short culture duration mightleave certain serum derived growth factors that was notconsumed by the cells and might add to the growth factorlevel or on the contrary suppress growth factor secretionby the cells Possibility of the presence of residual growthfactor from themedium can be seen in a study which showedthat medium without cell contained a TGF-b1 level of 249 plusmn239 pgmL (Table 3) [24]

33 Culture Condition Some studies produce CM fromcell culture in normoxia (O

2level 20-21) and variable

oxygen deprived (hypoxia O2level 05 1 15 and

2) condition (Table 2) Some studies on various stem cellsshowed thatmost growth factors were upregulated in hypoxiacondition for example vascular endothelial derived growthfactor (VEGF) [5 8 27] hepatocyte growth factor (HGF)[8 27] platelet derived growth factor (PDGF) [5 8] placentagrowth factor (PlGF) [25] and insulin-like growth factorII (IGF-II) [5] except epidermal growth factor (EGF) thatwas downregulated [5] However another study showed thecontrary that is down regulation of VEGF and HGF inhypoxia condition [25]

Most studies produced CM in monolayer culture butseveral studies used spheroid cultures (Table 3) Spheroid cul-tures need a special handling and equipment (spinner flask)but yield more cells compared to conventional monolayercultures and thus more secreted factors [6 24] (Table 4) Inaddition cells located at the center of the spheroid may be inrelative hypoxic condition compared to cells on the surfacethus further increasing certain growth factor yield

34 Secreted Factorrsquos Role in Improvement of Diseases Var-ious cytokines were secreted by stem cells into the CMand they played a role in the improvement of variousdiseasesconditions Those cytokines can be grouped intogrowth factors proinflammatory and anti-inflammatorycytokines and other cytokines Various studies used variousmethods to assess various cytokines in the conditioned CMfrom the conventional ELISA assays [6 10 24 25 27 33 36]to proteomic profiling methods [5 7ndash9 13 17 20 22 28 3435]

341 Growth Factors Growth factors that are secreted byvarious kinds of stem cells are vascular endothelial derivedgrowth factor (VEGF) [5 6 8 10 13 17 24 25 27 3336] platelet derived growth factor (PDGF) [5 8 10 1324] epidermal growth factor (EGF) [5 10 13 20] insulin-like growth factor I (IGF-I) [33 36] insulin-like growthfactor II (IGF-II) [5] hepatocyte growth factor (HGF) [68 20 25 27 33] fibroblast growth factor 2basic fibroblastgrowth factor (FGF-2bFGF) [6 7 10 13] keratinocytegrowth factorfibroblast growth factor 7 (KGFFGF-7) [1020] platelet derived endothelial cell growth factor (PDEGF)[20] heparin binding epidermal growth factor (HEGF) [20]placenta growth factor (PlGF) [25] neural growth factor(NGF) [28] and brain derived neurotrophic factor (BDNF)[28]

Further studies that analyzed various growth factorsreported the presence of the various growth factors whichwere secreted by various stem cells into their conditionedmedium (Table 3) except for human MSC (Lonza) that didnot secrete FGF-2 PDGFBB BMP-2 and SDF-1 but secretedIGF-1 VEGF TGF 1205731 and HGF [33] Moreover differentculture condition and medium may yield different level ofgrowth factor secretions [6]

342 Pro- and Anti-Inflammatory Cytokines Anti-inflam-matory cytokines that are secreted by stem cells are TGF1205731[9 10 20 24 33] and some interleukins (IL) that is IL-6 [9 13 17 25 28] IL-10 IL-27 IL-17E IL-13 IL-12p70and IL-1 receptor antagonist (IL-1ra) [20] while the secretedproinflammatory cytokines are IL-8CXCL-8 [8 9 13] IL-9[13 35] and IL-1b [20]

343 Other Cytokines Other secreted factors are leptin [7]angiogenin [8] granulocyte colony stimulating factor (GCSF)[5 10] granulocyte macrophage CSF (GM-CSF) [5 10 13]macrophage CSF (MCSF) [5] fractalkine [13] monocytechemotactic protein (MCP-1) [9 13 17 20] serpin E-1 [20]endostatincollegen XVIII [20] UPA thrombospondins 1and 2 [20] tissue inhibitor of metalloproteinase-1 (TIMP-1)[20] IGF binding protein (IGFBP) [5 20] stem cell-derivedfactor 1 (SDF-1)CXCL-12 [6ndash9 20 25] adrenomedullin(ADM) [25] Dickkopf-1 (DKK-1) [25] and receptors that is


Table2Celltypemediumculture

cond

ition

celln

umberdu

ratio

npassageandprocessin

gof

cond

ition

edmedium

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[7]

Hu-ES

C-EC

HUVEC

EBM2

NA

NA

5days

NA

NA

[13]

(i)Hu-ES

C-CD

133KD

R-EP

C(ii)H

u-UCB

-EPC

EGM-2

(Lon

za)mdash

15mL

150m

mcultu

redish

NA

80

48ho

urs

P5ndash8

Con

c50x

10kD

[16]

[29]

Hu-ES

C-MSC

Hu-ES

C-MSC

DMEM

mdashinsulin

transferrin

seleno

protein

FGF2P

DGF-AB

glutam

ineand120573-M

E

NA

NA

NA

NA

3days

3days

ge80

PD80

PDCon

c25x10kD

mdash220n

mrarr

05m

gmLprotein

[18]

Hu-ES

C-MSC

Chem

icallydefin

edmedium

NA

NA

3days

80PD

Con

c25x

10kD119886

[9]

Hu-AFSC

mdashCk

it(+)

120572MEM

Six-wellplate

5CO

215000

070

16ho

urs

NA

from

50000

0cellsmdash1m

LmdashCon

crarr

80120583L

[20]

1-Hu-AF-MSC

2-hu

-AF-MSC

-HPL

DMEM

05

FBS

25cm

2TC

flask

5CO

215times10

6

80

24ho

urs

P5ndash13

Con

c25x

3kD

[8]

(i)Hu-PB

-MNC-

EPC

(ii)H

UVEC

EBM2(Lon

za)1FB

S15

O

25

CONA

72ho

urs

NA

NA

[15]

PorcineP

B-MNC-

EPC

Exvivo

15(Lon

za)mdash

VEG

F1n

gmLmdash

FCplate

5CO

2From

30ndash4

0mL

PB48

hours

P0Centr

600g

5min02120583mmdashice

[12]

Hu-UC-

MSC

M199

5CO

2NA

24ho

urs

P3Con

c-02120583

m

[10]

(i)Hu-UCB

-MNC-

SC(end

othelial+

MSC

)(ii)H

UVEC

EGM-2ndash15m

L150m

mcultu

redish

5CO

280

48ho

urs

P5ndash8

Con

c50xmdash

10kD

[11]

Hu-UCB

-CD34-EPC

M199basalm

edium

5CO

21times

106

24ho

urs

NA

Con

c

[30]

(i)Hu-UCB

-USSC

(ii)m

BM-M

SCUltraC

ULT

URE

medium

75

BABL

cserum

5CO

260

48ho

urs

NA

NA

[14]

Hu-BM

-MSC

120572MEM

10FB

S5

CO2

2times10

7 flask

60ndash70

Till60ndash70

P5Con

c50xmdash

5kD

5flaskrarr

100120583

L[22]

Hu-BM

-MSC

NA-

005BS

ANA

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[26]

Hu-BM

-MSC

DMEM

-005

BSA

norm

oxia

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[27]

Hu-BM

-MSC

DMEM

-005

BSA

5CO

205

O2

2times10

6rarr

split

12

rarrconfl

24ho

urs

P3ndash7

Con

c25x

3kD

[17]

Hu-BM

-MNC-

stro-3-MPC

120572MEM

NA

1times10

6MPC

NA

P5Con

c

[25]

(i)Hu-BM

-MSC

(ii)H

u-BM

-CD133

(iii)Hu-BM

-p75

(iv)H

u-fib

ro

120572MEM

5CO

2(i)

1O

2(ii)2

1O

2

1times10

6

90

48ho

urs

P4-5

02120583

mmdash80∘C

conc40xmdash5k

D

[28]

Rat-B

M-M

SCDMEM

T75flask

NA

90

48ho

urs

P2ndash4

Con

c40xmdash

10kD

10m

Lrarr

250120583

L022120583mmdash80∘C


Table2Con

tinued

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[19]

RatB

M-M

SCDMEM

-005

BSA

10mL

NA

80ndash9

012

hours

P3-4

Con

c25x

3kD

[23]

(i)Hu-SC

-EDT

(ii)B

M-M

SC(Lon

za)

DMEM

5CO

24times10

548

hours

P3ndash5

3000

rpmmdash3m

inrarr

supernatant

[3]

Hu-AD-M

SCNA

Hypoxia

NA

NA

NA

Con

c-fre

ezed

ried

[24]

Hu-AD-M

SC120572MEM

70mL

Spheroid

1O

2mdash5

CO2

42times107

2days

NA

Centr

[6]

Hu-AD-SC

CRM120572MEM

CRMmdashhu

allo10

120572MEM

mdashFB

S10

1O

2mdash5

CO2

25ndash3times

105 mLmdash

24mLmdash

150c

mdish

2days

Upto

P5Centr

CRM120572MEM

CRMmdashhu

allo10

120572MEM

FBS10

Spheroid

1O

2mdash5

CO2

6ndash12times

105 mLmdash

30120583L

rarr70

mLflask

[1]

Hu-AD-SC

NA

NA

Reference[1314]

1times10

5rarr

80

24ho

urs

NA

Centr

300g

5minmdash220n

m

[5]

Hu-AD-SC

DMEM

F12

2O

25

CO2

4times10

572

hours

P4-5

Centr

300g

5rsquo022120583m3

kD

[23]

Hu-MSC

DMEM

-005

BSA

15mLmdash

175c

m2flask

NA

1times10

6

70ndash80

24ho

urs

NA

Con

c25x3k

D

[31]

Hu-MSC

(cellline)

DMEM

-10

FBS

5mL

5CO

270

48ho

urs

NA

10000

0gmdash

1hou

rrarr

supernatant

022120583m

[33]

Hu-MSC

(Lon

za)

DMEM

5CO

270

48ho

urs

P3ndash9

4∘Corminus80∘C

[32]

Mou

se-iP

SCNA

NA

NA

NA

NA

NA

Hu

humanE

SCembryonicste

mcell

ECend

othelialcellHUVEC

hum

anum

bilical

vein

endo

thelialcellEP

Cendo

thelialp

rogenitorcell

AF

amniotic

fluidS

Cste

mcell

MSC

mesenchym

alSC

HPL

hepatic

progenito

r-lik

ecell

ADadipo

setissuederiv

edP

Bperip

heralb

lood

MNC

mon

onuclear

cell

UC

umbilicalcordU

CBU

Cbloo

dmm

ouseB

Mb

onemarrow

MPC

mesenchym

alprogenito

rcell

fibrofibrob

last

EDT

exfoliateddecidu

oustoo

thiPS

Cindu

cedpluripotentS

CTC

tissue

cultu

reN

Anot

availableFB

Sfetalbovines

erum

allo

allo

genics

erum

BSA

bovines

erum

albu

minlowastFiltered220n

mrarr

10nmrarr

100n

myield

ed10ndash220

nmversus

10ndash100

nm(lt1000

kD)v

ersus100ndash220

nm(gt1000

kD)FC

fibron

ectin

coatedP

passageP

Dpop

ulationdo

ublin

gCM

con

ditio

nedmediumcon

cconcentrated

centrcentrifugation


Table 3 Growth factor level from various cell sources culture duration cell number and processing of conditioned medium

Referencenumber Cell source Cultureduration Cell

numberprocessing Growth factor level

[7] Hu-ESC-EC Monolayer mdash5 days NA

Angiogenic cytokine VEGF SDF-1 PlGFleptin EGF bFGF and HGFCM DM-PAC lt CM cPACAngiogenic cytokine VEGF PDGFICAM-1 EGF and bFGF CM ESC-EC gtCM c-PAC = CM D-PAC

[13] (i) Hu-ESC-CD133KDR-EPC(ii) Hu-UCB-EPC

Monolayermdash48hours

80 in 150mmculture dishConc50x

EGF

ESC-EPC versus CB-EPC versusEGM-212584 versus 12654 versus9 pgmL

FGF-2 383 versus 652 versus 61Fractalkine 1605 versus 150 versus 133GM-CSF 755 versus 323 versus 313IL-6 4332 versus 1961 versus 2463IL-8 239030 versus 13629 versus 7IL-9 345 versus 42 versus 9IP-10 458 versus 513 versus 511MCP-1 63 versus 3201 versus 1902PDGF-AA 6667 versus 5568 versus 41PDGF-ABBB 17 versus 1884 versus 75VEGF 4265 versus 538 versus 42

[9] Hu-AF SCmdashCkit (+) Monolayermdash16hours

15 times104mdash70from 5 times105 cells Conc125x

VEGF IL-8SDF-1 1 ng170000 cell (1 120583g DNA)

IL-6 MCP-1 05 ng170000 cellTGF-b 02 ng170000 cellIFNg mdashIP-10 CXCL10 mdashIL-1a mdash

[20] (i) Hu-AF-MSC(ii) Hu-AF-MSC-HPL


15 times 10680Conc 25x

Proteome analysisHu-AF-MSC-HPL-CMAnti-inflammatory cytokine IL-10 IL-27IL-17E IL-13 IL-12p70 and IL-1raLiver protection MCP- 1 IL-1bHu-AF-MSC-HPL-CM AF-MSC-CMAnti-inflammatory cytokine TGF1205731Tissue repair serpin E1 SDF-1Angiogenesis VEGF PDEGF andendostatincollagen XVIIILiver regeneration UPA thrombospondin 1and 2 HEGF FGF-7 EGF and HGFAnti-apoptotic markers TIMP-1 IGFBP

[8](i) Hu-PB-MNC-EPC(ii) HUVEC

Monolayermdash72hours NA

IL-8CXCL8Hypox versusnorm

290907 plusmn 122794 pgmLversus 22821 plusmn 4063 pgmL

SDF-1CXCL12 60599 plusmn 6546 pgmLversus 31799 plusmn 4880 pgmL

HGF 5395 plusmn 1417 pgmLversus 3434 plusmn 748 pgmL

Angiogenin 1446 plusmn 682 pgmLversus 725 plusmn 158 pgmL

PDGF-BB 1116 plusmn 2702 pgmLversus 199 plusmn 22 pgmL

VEGF-A 255 plusmn 48 pgmLversus 114 plusmn 52 pgmL


Table 3 Continued



[10]

Hu-UCB SC(endothelial + MSC)

Monolayermdash48hours 80Conc 50x

EGF 3286 plusmn 419 pgmLVEGF 2463 plusmn 151 pgmLG-CSF 3615 plusmn 173 pgmLGM-CSF 3623 plusmn 345 pgmLTGF-1205731 PDGFbFGF and KGF =HUVEC

HUVEC Monolayermdash48hours 80Conc 50x

EGF UCB-SC-48XVEGF UCB-SC-42xG-CSF UCB-SC-37xGM-CSF UCB-SC-24x

[22] Hu-BM-MSC Monolayermdash24hours 2 times 106Conc 25x 69 from 174 prot tested (+)

(concentration NA)

[27] Hu-BM-MSC Monolayermdash24hours 4 times 106Conc 25x

VEGF

HGF

Normoxia 230 pgmLHypoxia 450 pgmLNormoxia 600 pgmLHypoxia 750 pgmL

[17] Hu-BM-MNC-stro-3-MPC NA 1 times 106Conc

IL-6 = 2x C 11804 plusmn 027 pgmLMCP-1 = 2x C 52189 plusmn 148 pgmLVEGF = 2x C 3395 plusmn 298 pgmL

[25](i) Hu-BM-MSC(ii) Hu-BM-CD133(iii) Hu-BM-p75



Secretioncell P75 versus CD133 versusBMMSC

IL6mdashnorm 38 versus 08 versus 06 fgIL6mdashhypox 025 = 025 versus 01 fgPlGFmdashnorm 0045 versus 001 versus 0 fgPlGFmdashhypox 0043 versus 0025 versus 015 fgADMmdashnorm 01 versus 005 versus 02 fgADMmdashhypox 58 versus 54 versus 115 fgVEGFmdashnorm 15 versus 10 versus 135 fgVEGFmdashhypox 07 versus 09 versus 095 fgSDF-1mdashnorm 135 versus 075 versus 015 fgSDF-1mdashhypox 04 versus 07 versus 10 fgHGFmdashnorm 084 versus 07 versus 025 fgHGFmdashhypox 001 versus 025 versus 001 fgDKK-Imdashnorm 4 versus 4 versus 45 fgDKK-1mdashhypox 68 versus 65 versus 105 fg

[28] Rat-BM-MSC Monolayermdash48hours

90T75Conc 40x

23 from 90 prot tested (+)NGF 356 plusmn 117 pgmLBDNF 208 plusmn 57 pgmLIL-6 427plusmn 168 pgmL

[24] Hu-AD-MSC Spheroidmdash2 days 42 times 107Centr

CM versus120572MEMhTGF-b1

1433 plusmn 671 versus 249 plusmn239 pgmL

hVEGF 101517 plusmn 17097 pgmL versusND

hPDGF-AA Both ND

[6]

Hu-AD-SCIn 120572MEMmdashFBS Spheroidmdash

2 days 105Centr

VEGF 144 plusmn 04 ngmLFGF2 132 plusmn 22 ngmLHGF 133 plusmn 23 ngmLCXCL12 166 plusmn 29 ngmL

In CRM-hu allo No diff gtlt 120572MEM-FBSIn CRM-serum (minus) GF lt

In 120572MEMmdashFBS Monolayermdash2days 105Centr GFltltlt

In CRM-hu allo GFltltlt


Table 3 Continued



[5] Hu-AD-SC Monolayermdash72 hours 4 times 105Conc

Spot density array hypox versus nomoxiaGCSF 1407 plusmn 384 versus 1013 plusmn 421GM-CSF 1353 plusmn 126 versus 1021 plusmn 144IGFBP-1 948 plusmn 044 versus 556 plusmn 044IGFBP-2 891 plusmn 002 versus 673 plusmn 031IGF-II 1062 plusmn 085 versus 461 plusmn 093M-CSF 1406 plusmn 013 versus 746 plusmn 169M-CSF R 909 plusmn 020 versus 331 plusmn 175PDGF R120573 1767 plusmn 132 versus 1147 plusmn 140PDGF-AA 1663 plusmn 133 versus 1214 plusmn 212VEGF 1347 plusmn 126 versus 559 plusmn 122EGF 1106 plusmn 245 versus 3414 plusmn 675

[36](i) AD-SC(ii) Hu dermalfibroblast

NA NA

AD-SCVEGF 81065 plusmn 5692 pg120583g DNAIGF-I 32833 plusmn 227 pg120583g DNA

Hu dermal fibroblastVEGF 284 plusmn 225 pg120583g DNAIGFI Undetectable

[33] Hu-MSC (Lonza) Monolayermdash48hours 70(mdash)

IGF-1 15156 plusmn 2118 pgmLVEGF 4658 plusmn 1088 pgmLTGF-b1 3398 plusmn 144 pgmLHGF 203 plusmn 79 pgmL

FGF-2 PDGFBB BMP-2 and SDF-1 (mdash)CRM clinically relevant med hu allo human allogenic serum MP microparticle ND not detected SDF-1 stromal derived factor-1 PlGF placental GFbFGF basic FGF HGF hepatocyte GF PAC peripheral blood angiogenic cells (from PBMN cells-floating) cPAC healthy control PAC ESC-EC ESC derivedendothelial cell MCP-1 monocyte chemotactic protein-1 PDEGF platelet derived endothelial cell GF UPA urokinase plasminogen activator HEGF heparinbinding epidermal GF TIMP-1 tissue inhibitor of metalloproteinase-1 IGFBP insulin-like GF binding protein IP-10 interferon inducible protein-1 ADMadrenomedullin DKK-1 Dickkopf-1 norm normoxic hypox = hypoxic fg = fentogram

MCSF receptor (MCSFR) [5] and PDGF receptor (PDGFR)[5]

35 Translation of Conditioned Medium Usage in PatientsIn conditioned medium various factors may be presentas a cocktail and act in concert to promote regenerationTherefore it is important to analyze a complete set of growthfactor and cytokine levels for every kind of stem cell-derivedconditionedmedium and to know the culture condition con-ditioned medium processing and diseasesconditions thatare responsive to a certain conditioned medium treatmentWhen the content of the various cytokines in a certainconditioned medium is known the result of the conditionedmedium on a certain diseasecondition can be determinedand the way to translation into patients is open

From studies that analyzed VEGF level we can concludethat most stem cells secrete VEGF As VEGF plays a roleon angiogenesis [36] that is important in regeneration ofinjureddamaged tissuesorgans various stem cell-derivedconditioned media are able to cure various diseases and willhave more impact on diseases with ischemia In additionVEGF may prevent apoptosis in hypoxic condition thuspreventing further damage [6]

Concerning angiogenesis other thanVEGF other growthfactors that may play a role in angiogenesis are FGF2 [7 38]EGF [7] HGF [7 8] PlGF [7] SDF-1 [7] PDGF [7 38]TGF1205731 [38] and PDEGF [39] In addition various cytokinesthat is interleukin [38] IL-8 [8 9 13] chemokines [38]monocyte chemotactic protein (MCP-1) [9 13 17 20] leptin[7] angiogenin [8] and endostatincollagen XVIII [20] alsoplay a role in angiogenesis

Moreover FGF2 is a more potent angiogenic factorcompared to VEGF with additional effect on proliferationof fibroblasts preadipocytes and endothelial epithelial andneural stem cells on migration of neural crest derived glialand myogenic cells and on differentiation of neuroepithelialcells into mature neurons and glial cells [38]

Other growth factors contribute in the regeneration ofinjureddamaged tissue organs with special emphasis on pro-liferation that is PDGF for connective tissue glial and othercells EGF for mesenchymal glial and epithelial cells andIGF-I and IGF-II for various kinds of cells [40] In additionPlGF that is a member of VEGF family increases the activityofVEGF in vitro and in vivo [41] KGF inhibits oxidative stressinduced epithelial cell death [42] NGF promotes neuriteoutgrowth and neural cell survival [40] BDNF is neuropro-tective promotes cell survival and reduces astroglial scar


Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7

daysmdashlateralventricle

Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB

AlopeciaSkin regenerationWound Cerebral ischemiastrokeBrainspinal cord injuryBonecartilage defectLiver failure

Myocardial infarct

Limb ischemia

MSC = mesenchymal stem cellCM = conditioned mediumPB = peripheral blood

UCB = umbilical cord bloodEPC = endothelial progenitor cell

Figure 1 Various possible applications of CM for various conditions

formation [28] and some growth factors including HEGFFGF-7 EGF and HGF promote liver regeneration [20]

Proinflammatory cytokines that play a role in regen-eration are IL-1b due to its liver protective role [20] IL-8 due to its angiogenic activity [8 9 13] and IL-9 due towound healing promotion activity [13 43] In addition anti-inflammatory cytokines prevent inflammation and promoteliver regeneration [20]

Other cytokines that is UPA and thrombospondins 1 and2 promote liver regeneration [20] serpin E-1 [20] and SDF-1[6ndash9 20 25] promote tissue repair [20] TIMP-1 and IGFBP[5 20] prevent apoptosis [20] ADM causes vasodilatationand reduces cellular oxidative stress and apoptosis [25]DKK-1 initiates bone marrow stem cell proliferation [25] andfractalkine prevents apoptosis [13 44]

Various colony stimulating factors that is granulocytecolony stimulating factor (GCSF) [5 10] granulocyte macro-phage CSF (GM-CSF) [5 10 13] and macrophage CSF(MCSF) [5] may recruit various resident stem cellspro-genitor cells including endothelial progenitors to site ofinjurydamage and promote wound healing process [10 13]or hair growth [5]

MCSF receptor (MCSFR) [5] promotes myeloid pro-genitor mononuclear phagocyte and placental trophoblastgrowth and development [45] and PDGFR [5] may interactwith various signalingmolecules or integrin to cause cell pro-liferation motility differentiation or survival by apoptosisinhibition [46]

Moreover one factor may contribute to more than onemode of regenerative action such as MCP-1 that is involvedin angiogenesis [9 13 17 20] and liver protection activity [20]Further for production of CM to be applied in various human

diseases data from animal studies that showed promisingoutcome are very valuable

351 Production of CM for Translation into Various HumanDiseases To use CM for various human diseases productionmethod of the CM needs to be standardized in terms of thetype andnumber of cells thatwere needed to produce theCMculture medium and condition and conditioned mediumprocessing In addition the volume and mode of deliveryare also important As various studies used various numbersand type of cells and various doses of CM it is importantto know the number of cells that yielded the CM for oneapplication which may be interpolated for human studiesTherefore in Table 4 we summarized all data that may beneeded for interpolation into human studies that is diseasesthat were treated species and age or body weight of theanimal type of cell culture medium and condition numberof cells to produceCM for one application volume andmodeof applicationMoreover various possible applications of CMfor various conditions are summarized in Figure 1

In addition for translation into patients it is very impor-tant to analyze and to note the various cytokine contentsof the various conditioned media Further for every condi-tioned medium with known cytokine content validation ofits use on various diseases needs to be conducted Finally thepossibility of promotion of existing cancer should be testedfor everyCM and caution should be taken beforeCM therapyto ensure that the recipient is free from cancer

Advantages of production of various CM for patientslie in the possibility of mass production by pharmaceuticalcompanies when production methods have been standard-ized Conditioned media are not like stem cells that need agood manufacturing practice (GMP) facility to be applied


to patients [47] When CM has been packaged properlyit can be transported easily as drugs and does not needcryopreservation such as that the stem cells need Howevercompared to stem cells that may survive for a rather longperiod CM needs to be given more frequently as cytokinesrsquoand growth factorsrsquo half-lives are mostly shorter [48 49]which is a disadvantage for the patients but will give moreprofit to pharmaceutical companies

4 Conclusion

Various stem cell-derived conditioned media were producedby various methods and processing and tested on variousdiseases and mostly showed good results However stan-dardized methods for various conditioned media productionand validations of their use on various diseases need to beconducted

Conflict of Interests

The author declares that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

This study was funded by the research grant from IndonesianMinistry of Education and Culture (Pusnas 2014) Contractno 2218H2R12HKP05002014

References

[1] D Yang W Wang L Li et al ldquoThe relative contribution ofparacine effect versus direct differentiation on adipose-derivedstem cell transplantation mediated cardiac repairrdquo PLoS ONEvol 8 no 3 Article ID e59020 2013

[2] H O Kim and S Choi ldquoMesenchymal stem cell-derivedsecretome and microvesicles as a cell-free therapeutics for neu-rodegenerative disordersrdquo Tissue Engineering and RegenerativeMedicine vol 10 no 3 pp 93ndash101 2013

[3] H Fukuoka H Suga K Narita R Watanabe and S ShintanildquoThe latest advance in hair regeneration therapy using proteinssecreted by adipose-derived stem cellsrdquo American Journal ofCosmetic Surgery vol 29 no 4 pp 273ndash282 2012

[4] B R Zhou Y Xu S L Guo et al ldquoThe effect of conditionedmedia of adipose-derived stem cells on wound healing afterablative fractional carbon dioxide laser resurfacingrdquo BioMedResearch International vol 2013 Article ID 519126 9 pages2013

[5] B S ParkW S Kim J S Choi et al ldquoHair growth stimulated byconditioned medium of adipose-derived stem cells is enhancedby hypoxia evidence of increased growth factor secretionrdquoBiomedical Research vol 31 no 1 pp 27ndash34 2010

[6] S H Bhang S Lee J Y Shin T J Lee H K Jang andB S Kim ldquoEfficacious and clinically relevant conditioned-medium of human adipose-derived stem cells for therapeuticangiogenesisrdquoMolecular Therapy vol 22 no 4 p 862 2014

[7] J C Y Ho W Lai M Li et al ldquoReversal of endothelialprogenitor cell dysfunction in patients with type 2 diabetes

using a conditioned medium of human embryonic stem cell-derived endothelial cellsrdquo DiabetesMetabolism Research andReviews vol 28 no 5 pp 462ndash473 2012

[8] S di Santo Z Yang M W von Ballmoos et al ldquoNovel cell-freestrategy for therapeutic angiogenesis in vitro generated con-ditioned medium can replace progenitor cell transplantationrdquoPLoS ONE vol 4 no 5 Article ID e5643 2009

[9] T Mirabella M Cilli S Carlone R Cancedda and C GentilildquoAmniotic liquid derived stem cells as reservoir of secretedangiogenic factors capable of stimulating neo-arteriogenesis inan ischemicmodelrdquo Biomaterials vol 32 no 15 pp 3689ndash36992011

[10] J Kim J H Lee S M Yeo H M Chung and J I Chae ldquoStemcell recruitment factors secreted from cord blood-derived stemcells that are not secreted frommature endothelial cells enhancewound healingrdquo In Vitro Cellular amp Developmental BiologyAnimal vol 50 no 2 pp 146ndash154 2014

[11] J Y Kim S H Song K L Kim et al ldquoHuman cord blood-derived endothelial progenitor cells and their conditionedmedia exhibit therapeutic equivalence for diabetic woundhealingrdquo Cell Transplantation vol 19 no 12 pp 1635ndash16442010

[12] C Shrestha L Zhao K Chen H He and Z Mo ldquoEnhancedhealing of diabetic wounds by subcutaneous administration ofhuman umbilical cord derived stem cells and their conditionedmediardquo International Journal of Endocrinology vol 2013 ArticleID 592454 10 pages 2013

[13] M J Lee J Kim K I Lee J M Shin J I Chae and H MChung ldquoEnhancement of wound healing by secretory factorsof endothelial precursor cells derived from human embryonicstem cellsrdquo Cytotherapy vol 13 no 2 pp 165ndash178 2011

[14] P J Mishra and D Banerjee ldquoCell-free derivatives from mes-enchymal stem cells are effective in wound therapyrdquo WorldJournal of Stem Cells vol 4 no 5 pp 35ndash43 2012

[15] B Hynes A H S Kumar J OrsquoSullivan et al ldquoPotent endothelialprogenitor cell-conditioned media-related anti-apoptotic car-diotrophic and pro-angiogenic effects post-myocardial infarc-tion are mediated by insulin-like growth factor-1rdquo EuropeanHeart Journal vol 34 no 10 pp 782ndash789 2013

[16] L Timmers S K Lim I E Hoefer et al ldquoHuman mesenchy-mal stem cell-conditioned medium improves cardiac functionfollowing myocardial infarctionrdquo Stem Cell Research vol 6 no3 pp 206ndash214 2011

[17] F See T Seki P J Psaltis et al ldquoTherapeutic effects ofhumanSTRO-3-selectedmesenchymal precursor cells and theirsoluble factors in experimental myocardial ischemiardquo Journal ofCellular and Molecular Medicine vol 15 no 10 pp 2117ndash21292011

[18] L Timmers S K Lim F Arslan et al ldquoReduction ofmyocardialinfarct size by human mesenchymal stem cell conditionedmediumrdquo Stem Cell Research vol 1 no 2 pp 129ndash137 2008

[19] Z Du C Wei K Cheng et al ldquoMesenchymal stem cell-conditioned medium reduces liver injury and enhances regen-eration in reduced-size rat liver transplantationrdquo Journal ofSurgical Research vol 183 no 2 pp 907ndash915 2013

[20] D S Zagoura M G Roubelakis V Bitsika et al ldquoTherapeuticpotential of a distinct population of human amniotic fluidmesenchymal stem cells and their secreted molecules in micewith acute hepatic failurerdquoGut vol 61 no 6 pp 894ndash906 2012


[21] D van Poll B Parekkadan CH Cho et al ldquoMesenchymal stemcell-derived molecules directly modulate hepatocellular deathand regeneration in vitro and in vivordquoHepatology vol 47 no 5pp 1634ndash1643 2008

[22] B Parekkadan D Van Poll K Suganuma et al ldquoMesenchymalstem cell-derived molecules reverse fulminant hepatic failurerdquoPLoS ONE vol 2 no 9 article e941 2007

[23] T Inoue M Sugiyama H Hattori H Wakita T Wakabayashiand M Ueda ldquoStem cells from human exfoliated deciduoustooth-derived conditioned medium enhance recovery of focalcerebral ischemia in ratsrdquo Tissue Engineering A vol 19 no 1-2pp 24ndash29 2013

[24] Y J Cho H S Song S Bhang et al ldquoTherapeutic effectsof human adipose stem cell-conditioned medium on strokerdquoJournal of Neuroscience Research vol 90 no 9 pp 1794ndash18022012

[25] B Bakondi I S Shimada A Perry et al ldquoCD133 identifiesa human bone marrow stemprogenitor cell sub-populationwith a repertoire of secreted factors that protect against strokerdquoMolecular Therapy vol 17 no 11 pp 1938ndash1947 2009

[26] T J Chuang K C Lin C C Chio C C Wang C P Changand J R Kuo ldquoEffects of secretome obtained from normoxia-preconditioned human mesenchymal stem cells in traumaticbrain injury ratsrdquo Journal of Trauma and Acute Care Surgeryvol 73 no 5 pp 1161ndash1167 2012

[27] C Chang C Chio C Cheong C Chao B Cheng and M LinldquoHypoxic preconditioning enhances the therapeutic potential ofthe secretome from cultured humanmesenchymal stem cells inexperimental traumatic brain injuryrdquo Clinical Science vol 124no 3 pp 165ndash176 2013

[28] D Cantinieaux R Quertainmont S Blacher et al ldquoCondi-tionedmedium from bonemarrow-derived mesenchymal stemcells improves recovery after spinal cord injury in rats anoriginal strategy to avoid cell transplantationrdquo PLoS ONE vol8 no 8 Article ID e69515 2013

[29] A van Koppen J A Joles B W M van Balkom et alldquoHuman embryonic mesenchymal stem cell-derived condi-tionedmedium rescues kidney function in rats with establishedchronic kidney diseaserdquo PLoS ONE vol 7 no 6 Article IDe38746 2012

[30] Y Gheisari N Ahmadbeigi M Naderi S M Nassiri S Nadriand M Soleimani ldquoStem cell-conditioned medium does notprotect against kidney failurerdquo Cell Biology International vol35 no 3 pp 209ndash213 2011

[31] W Zhu L Huang Y Li et al ldquoMesenchymal stem cell-secretedsoluble signaling molecules potentiate tumor growthrdquo CellCycle vol 10 no 18 pp 3198ndash3207 2011

[32] L Li Y Liu C Yang et al ldquoImprovement of ventilator-inducedlung injury by IPS cell-derived conditioned medium via inhi-bition of PI3KAkt pathway and IP-10-dependent paracrineregulationrdquo Biomaterials vol 34 no 1 pp 78ndash91 2013

[33] T Inukai W Katagiri R Yoshimi et al ldquoNovel applicationof stem cell-derived factors for periodontal regenerationrdquo Bio-chemical and Biophysical Research Communications vol 430no 2 pp 763ndash768 2013

[34] E Ivanova-Todorova I Bochev R Dimitrov et al ldquoCondi-tionedmedium from adipose tissue-derivedmesenchymal stemcells induces CD4+FOXP3+ cells and increases IL-10 secretionrdquoJournal of Biomedicine and Biotechnology vol 2012 Article ID295167 8 pages 2012

[35] S K Sze D P V de Kleijn R C Lai et al ldquoElucidatingthe secretion proteome of human embryonic stem cell-derivedmesenchymal stem cellsrdquo Molecular and Cellular Proteomicsvol 6 no 10 pp 1680ndash1689 2007

[36] S Sadat S Gehmert Y Song et al ldquoThe cardioprotective effectof mesenchymal stem cells is mediated by IGF-I and VEGFrdquoBiochemical and Biophysical Research Communications vol 363no 3 pp 674ndash679 2007

[37] R Goswami and M H Kaplan ldquoA brief history of IL-9rdquo TheJournal of Immunology vol 186 no 6 pp 3283ndash3288 2011

[38] Y R Yun J E Won E Jeon et al ldquoFibroblast growth factorsbiology function and application for tissue regenerationrdquoJournal of Tissue Engineering vol 2010 Article ID 218142 2010

[39] T Saeki M Tanada S Takashima et al ldquoCorrelation betweenexpression of platelet-derived endothelial cell growth factor(thymidine phosphorylase ) and microvessel density in early-stage human colon carcinomasrdquo Japanese Journal of ClinicalOncology vol 27 no 4 pp 227ndash230 1997

[40] G Litwack ldquoGrowth factors and cytokinesrdquo in Human Bio-chemistry and Disease G Litwack Ed pp 587ndash683 ElsevierAcademic Press 2008

[41] J E Park H H Chen J Winer K A Houck and N FerraraldquoPlacenta growth factor potentiation of vascular endothelialgrowth factor bioactivity in vitro and in vivo and high affinitybinding to Flt-1 but not to Flk-1KDRrdquoThe Journal of BiologicalChemistry vol 269 no 41 pp 25646ndash25654 1994

[42] P Ray Y Devaux D B Stolz et al ldquoInducible expressionof keratinocyte growth factor (KGF) in mice inhibits lungepithelial cell death induced by hyperoxiardquo Proceedings of theNational Academy of Sciences of the United States of Americavol 100 no 10 pp 6098ndash6103 2003

[43] J E Turner P J Morrison C Wilhelm et al ldquoIL-9-mediatedsurvival of type 2 innate lymphoid cells promotes damagecontrol in helminthmdashinduced lung inflammationrdquoThe Journalof Experimental Medicine vol 210 no 13 pp 2951ndash2965 2013

[44] G E White and D R Greaves ldquoFractalkine a survivorrsquosguide chemokines as antiapoptotic mediatorsrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 3 pp 589ndash5942012

[45] A Mancini A Koch A D Whetton and T Tamura ldquoTheM-CSF receptor substrate and interacting protein FMIP isgoverned in its subcellular localization by protein kinase C-mediated phosphorylation and thereby potentiates M-CSF-mediated differentiationrdquo Oncogene vol 23 no 39 pp 6581ndash6589 2004

[46] J Andrae R Gallini and C Betsholtz ldquoRole of platelet-derived growth factors in physiology and medicinerdquo Genes andDevelopment vol 22 no 10 pp 1276ndash1312 2008

[47] P Wuchter K Bieback H Schrezenmeier et al ldquoStandardiza-tion of GoodManufacturing Practicendashcompliant production ofbone marrowndashderived human mesenchymal stromal cells forimmunotherapeutic applicationsrdquo Cytotherapy 2014

[48] P Yde B Mengel M H Jensen S Krishna and A TrusinaldquoModeling the NF-120581B mediated inflammatory response pre-dicts cytokine waves in tissuerdquo BMC Systems Biology vol 5article 115 2011

[49] A Khosravi C M Cutler M H Kelly et al ldquoDeterminationof the elimination half-life of fibroblast growth factor-23rdquo TheJournal of Clinical Endocrinology amp Metabolism vol 92 no 6pp 2374ndash2377 2007


the various methods to get the CM and the various diseasesthat were treated to get an insight into the various kinds ofCM and their application benefit in various diseases

2 Materials and Methods

We performed ldquoall textrdquo searches without time restrictionon January 23 2014 in PubmedMedline using keywordsldquostem cellrdquo and ldquoconditioned mediumrdquo or ldquosecretomerdquo andldquotherapyrdquo ldquoall textrdquo searches in Cochrane library (trials) usingkeywords ldquosecretomerdquo or ldquoconditioned mediumrdquo and ldquoalltextrdquo searches in ClinicalTrialsgov using keywords ldquostemcellrdquo and ldquoconditionedmediumrdquo or ldquosecretomerdquo and ldquotherapyrdquoIn addition relevant existing articles in our library wereadded

Inclusion criteria are all studies that usedCM for a certaindisease Exclusion criteria are studies that did not containcomplete data concerning subject conditiondisease modelsource of CM and outcome of treatment with CM

Data collection is as follows treated conditionsdiseasestype of cell that was cultured detailed composition ofmedium and supplements that was used to culture the cellsculture condition (hypoxia or normoxia) to get the CM CMprocessing growth factors and other secretions that wereanalyzed method (mode) of application and outcome of CMapplication were noted grouped and tabulated

Data synthesis is as follows data were grouped accordingto treated disease and cell types that were used to producethe CM Further to know the growth factor yields of thevarious types of cells when available growth factor levelswere tabulated and grouped according to types of cells thatyielded the growth factor containing conditionedmedium inrelation to the number of cells type and duration of cultureand processing of the conditioned medium When the datawas available the number of cells thatwere needed to producethe CM for one application was computed

3 Results and Discussion

We got 39 articles that met the inclusion criteria and 7 wereexcluded due to incomplete data Various conditionsdiseaseswere treated by various cell-derived CM and mostly showedpromising results (Table 1)

The various conditioned media even when they werederived from same kind of cells were produced by differentcondition that is from different passage number of cellsculture medium and culture condition (Table 2)The growthfactor yields of the various types of cells can be seen inTable 3and the cell number that is needed to produce CM for oneapplication can be seen in Table 4

Various studies showed that conditioned medium havebeen tested in various kinds of diseasesconditions (Table 1)[1 3ndash33] that is alopecia [3 5] acute and chronic hind limbischemia [6ndash9] acute and chronic wound healing [4 10ndash14] myocardial infarct [1 15ndash18] acute liver injuryfailure[19ndash22] cerebral injuryischemiastroke [23ndash27] spinal cordinjury [28] lung injury [32] and bone defect [33] and

showed improvement of the conditions Moreover chronickidney disease that was treated using human embryonicstem cell-derived mesenchymal stem cell (huESC-MSC) CMshowed decreased systolic blood pressure and proteinuriaand improvement in tubular and glomerular damage renalblood flow and glomerular filtration rate [29] Howevernephropathy that was treated using CM from human umbili-cal cord blood unrestricted somatic stem cell (huUCB-USSC)or mouse bonemarrowmesenchymal stem cell (mBM-MSC)CM did not show improvement in serum urea and creati-nine level histopathological damage and physical activityscore [30] Moreover prevention of cancer using humanmesenchymal stem cell line CM showed increased tumor cellproliferation and vascularization [31]

In the two cases of kidney disease it can be concludedthat CM from hu-ESC-MSC can improve the condition andthe needed growth factor level is presumably enough asCM processing includes a 25-time concentration step [29]However for hu-UCB-USSC ormBM-MSC-CM lack of dataconcerning CMprocessing and growth factor level of the CM[30] prevent further analysis to conclude whether the failureto improve the condition is due to the lack of certain growthfactor or due to the level of growth factors that was too low togive an effect

The conditioned medium can be harvested from variouskinds of cells (Table 2) Moreover there are various methodsto get the conditioned medium which may interfere withthe growth factor types and levels that were harvested bythe methods Only some of the various studies using CMchecked the growth factor levels (Table 3) [5ndash10 13 17 2022 24 25 27 28 33 36] and the same type of cells yieldeddifferent growth factor levels when cell number culturemedium and condition and CM processing were different[6 24] Moreover growth factor measures also differed thatis pgmL or ngmL [6 8 10 13 17 24 27 28 33] pg120583g DNA[9 36] fgcell [25] spot density [5] and positivenegative[20] (Table 3) The measure of pg120583g DNA and fgcell can becomputed into pg or ngmL provided the DNA contentcelland cell number is known However in some studies theexact cell number that was used to produce the CM wasnot mentioned [7 8 10 13 28 33 36] In addition moststudies measured different sets of growth factors and othercytokinesfactors (Table 3)

31 Culture Medium and Supplement Some studies usedfetal bovine serum or other supplement containing completemedium while other studies used serum-free media More-over the basalmedia usedwere variable for example120572MEMDMEM DMEMF12 M199 EBM2 EGM-2 in vivo 15or chemically defined medium and the same type of cellmight be cultured in different kind of basalmedium (Table 2)Culture medium in in vitro culture represents microenvi-ronment in in vivo condition and may determine cell fateand thus cell secretion [37] Therefore the same type ofcells may secrete different level of growth factors when theywere cultured in different medium as can be seen in Table 3[25 27]








[6]



[7]





[9]



BALBc nude mice



[10]



[11]





[13]





[1]



[15]



[16]



[17]








Table 1 Continued






[20]


Male SD rat Hu-MSC


[21]



[22]




[23]




[24]





[25]




[26]



[27]





[29]


(ii) Mouse BM-MSC


[30]



[31]



[32]


Table 1 Continued


















cond

ition

celln

umberdu

ratio


gof

cond

ition

edmedium

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[7]

Hu-ES

C-EC

HUVEC

EBM2

NA

NA

5days

NA

NA

[13]

(i)Hu-ES

C-CD

133KD

R-EP

C(ii)H

u-UCB

-EPC

EGM-2

(Lon

za)mdash

15mL

150m

mcultu

redish

NA

80

48ho

urs

P5ndash8

Con

c50x

10kD

[16]

[29]

Hu-ES

C-MSC

Hu-ES

C-MSC

DMEM

mdashinsulin

transferrin

seleno

protein

FGF2P

DGF-AB

glutam

ineand120573-M

E

NA

NA

NA

NA

3days

3days

ge80

PD80

PDCon

c25x10kD

mdash220n

mrarr

05m

gmLprotein

[18]

Hu-ES

C-MSC

Chem

icallydefin

edmedium

NA

NA

3days

80PD

Con

c25x

10kD119886

[9]

Hu-AFSC

mdashCk

it(+)

120572MEM

Six-wellplate

5CO

215000

070

16ho

urs

NA

from

50000

0cellsmdash1m

LmdashCon

crarr

80120583L

[20]

1-Hu-AF-MSC

2-hu

-AF-MSC

-HPL

DMEM

05

FBS

25cm

2TC

flask

5CO

215times10

6

80

24ho

urs

P5ndash13

Con

c25x

3kD

[8]

(i)Hu-PB

-MNC-

EPC

(ii)H

UVEC

EBM2(Lon

za)1FB

S15

O

25

CONA

72ho

urs

NA

NA

[15]

PorcineP

B-MNC-

EPC

Exvivo

15(Lon

za)mdash

VEG

F1n

gmLmdash

FCplate

5CO

2From

30ndash4

0mL

PB48

hours

P0Centr

600g


[12]

Hu-UC-

MSC

M199

5CO

2NA

24ho

urs

P3Con

c-02120583

m

[10]

(i)Hu-UCB

-MNC-

SC(end

othelial+

MSC

)(ii)H

UVEC

EGM-2ndash15m

L150m

mcultu

redish

5CO

280

48ho

urs

P5ndash8

Con

c50xmdash

10kD

[11]

Hu-UCB

-CD34-EPC

M199basalm

edium

5CO

21times

106

24ho

urs

NA

Con

c

[30]

(i)Hu-UCB

-USSC

(ii)m

BM-M

SCUltraC

ULT

URE

medium

75

BABL

cserum

5CO

260

48ho

urs

NA

NA

[14]

Hu-BM

-MSC

120572MEM

10FB

S5

CO2

2times10

7 flask

60ndash70

Till60ndash70

P5Con

c50xmdash

5kD

5flaskrarr

100120583

L[22]

Hu-BM

-MSC

NA-

005BS

ANA

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[26]

Hu-BM

-MSC

DMEM

-005

BSA

norm

oxia

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[27]

Hu-BM

-MSC

DMEM

-005

BSA

5CO

205

O2

2times10

6rarr

split

12

rarrconfl

24ho

urs

P3ndash7

Con

c25x

3kD

[17]

Hu-BM

-MNC-

stro-3-MPC

120572MEM

NA

1times10

6MPC

NA

P5Con

c

[25]

(i)Hu-BM

-MSC

(ii)H

u-BM

-CD133

(iii)Hu-BM

-p75

(iv)H

u-fib

ro

120572MEM

5CO

2(i)

1O

2(ii)2

1O

2

1times10

6

90

48ho

urs

P4-5

02120583

mmdash80∘C

conc40xmdash5k

D

[28]

Rat-B

M-M

SCDMEM

T75flask

NA

90

48ho

urs

P2ndash4

Con

c40xmdash

10kD

10m

Lrarr

250120583



Table2Con

tinued

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[19]

RatB

M-M

SCDMEM

-005

BSA

10mL

NA

80ndash9

012

hours

P3-4

Con

c25x

3kD

[23]

(i)Hu-SC

-EDT

(ii)B

M-M

SC(Lon

za)

DMEM

5CO

24times10

548

hours

P3ndash5

3000

rpmmdash3m

inrarr

supernatant

[3]

Hu-AD-M

SCNA

Hypoxia

NA

NA

NA

Con

c-fre

ezed

ried

[24]

Hu-AD-M

SC120572MEM

70mL

Spheroid

1O

2mdash5

CO2

42times107

2days

NA

Centr

[6]

Hu-AD-SC

CRM120572MEM

CRMmdashhu

allo10

120572MEM

mdashFB

S10

1O

2mdash5

CO2

25ndash3times

105 mLmdash

24mLmdash

150c

mdish

2days

Upto

P5Centr

CRM120572MEM

CRMmdashhu

allo10

120572MEM

FBS10

Spheroid

1O

2mdash5

CO2

6ndash12times

105 mLmdash

30120583L

rarr70

mLflask

[1]

Hu-AD-SC

NA

NA

Reference[1314]

1times10

5rarr

80

24ho

urs

NA

Centr

300g

5minmdash220n

m

[5]

Hu-AD-SC

DMEM

F12

2O

25

CO2

4times10

572

hours

P4-5

Centr

300g

5rsquo022120583m3

kD

[23]

Hu-MSC

DMEM

-005

BSA

15mLmdash

175c

m2flask

NA

1times10

6

70ndash80

24ho

urs

NA

Con

c25x3k

D

[31]

Hu-MSC

(cellline)

DMEM

-10

FBS

5mL

5CO

270

48ho

urs

NA

10000

0gmdash

1hou

rrarr

supernatant

022120583m

[33]

Hu-MSC

(Lon

za)

DMEM

5CO

270

48ho

urs

P3ndash9

4∘Corminus80∘C

[32]

Mou

se-iP

SCNA

NA

NA

NA

NA

NA

Hu

humanE

SCembryonicste

mcell

ECend

othelialcellHUVEC

hum

anum

bilical

vein

endo

thelialcellEP

Cendo

thelialp

rogenitorcell

AF

amniotic

fluidS

Cste

mcell

MSC

mesenchym

alSC

HPL

hepatic

progenito

r-lik

ecell

ADadipo

setissuederiv

edP

Bperip

heralb

lood

MNC

mon

onuclear

cell

UC

umbilicalcordU

CBU

Cbloo

dmm

ouseB

Mb

onemarrow

MPC

mesenchym

alprogenito

rcell

fibrofibrob

last

EDT

exfoliateddecidu

oustoo

thiPS

Cindu

cedpluripotentS

CTC

tissue

cultu

reN

Anot

availableFB

Sfetalbovines

erum

allo

allo

genics

erum

BSA

bovines

erum

albu


mrarr

10nmrarr

100n

myield

ed10ndash220

nmversus

10ndash100

nm(lt1000

kD)v

ersus100ndash220

nm(gt1000

kD)FC

fibron

ectin

coatedP

passageP

Dpop

ulationdo

ublin

gCM

con

ditio

nedmediumcon

cconcentrated

centrcentrifugation










EGF





















Table 3 Continued



[10]







(concentration NA)


VEGF

HGF










90T75Conc 40x






hPDGF-AA Both ND

[6]


2 days 105Centr






Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References



























































[6]



[7]





[9]



BALBc nude mice



[10]



[11]





[13]





[1]



[15]



[16]



[17]








Table 1 Continued






[20]


Male SD rat Hu-MSC


[21]



[22]




[23]




[24]





[25]




[26]



[27]





[29]


(ii) Mouse BM-MSC


[30]



[31]



[32]


Table 1 Continued


















cond

ition

celln

umberdu

ratio


gof

cond

ition

edmedium

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[7]

Hu-ES

C-EC

HUVEC

EBM2

NA

NA

5days

NA

NA

[13]

(i)Hu-ES

C-CD

133KD

R-EP

C(ii)H

u-UCB

-EPC

EGM-2

(Lon

za)mdash

15mL

150m

mcultu

redish

NA

80

48ho

urs

P5ndash8

Con

c50x

10kD

[16]

[29]

Hu-ES

C-MSC

Hu-ES

C-MSC

DMEM

mdashinsulin

transferrin

seleno

protein

FGF2P

DGF-AB

glutam

ineand120573-M

E

NA

NA

NA

NA

3days

3days

ge80

PD80

PDCon

c25x10kD

mdash220n

mrarr

05m

gmLprotein

[18]

Hu-ES

C-MSC

Chem

icallydefin

edmedium

NA

NA

3days

80PD

Con

c25x

10kD119886

[9]

Hu-AFSC

mdashCk

it(+)

120572MEM

Six-wellplate

5CO

215000

070

16ho

urs

NA

from

50000

0cellsmdash1m

LmdashCon

crarr

80120583L

[20]

1-Hu-AF-MSC

2-hu

-AF-MSC

-HPL

DMEM

05

FBS

25cm

2TC

flask

5CO

215times10

6

80

24ho

urs

P5ndash13

Con

c25x

3kD

[8]

(i)Hu-PB

-MNC-

EPC

(ii)H

UVEC

EBM2(Lon

za)1FB

S15

O

25

CONA

72ho

urs

NA

NA

[15]

PorcineP

B-MNC-

EPC

Exvivo

15(Lon

za)mdash

VEG

F1n

gmLmdash

FCplate

5CO

2From

30ndash4

0mL

PB48

hours

P0Centr

600g


[12]

Hu-UC-

MSC

M199

5CO

2NA

24ho

urs

P3Con

c-02120583

m

[10]

(i)Hu-UCB

-MNC-

SC(end

othelial+

MSC

)(ii)H

UVEC

EGM-2ndash15m

L150m

mcultu

redish

5CO

280

48ho

urs

P5ndash8

Con

c50xmdash

10kD

[11]

Hu-UCB

-CD34-EPC

M199basalm

edium

5CO

21times

106

24ho

urs

NA

Con

c

[30]

(i)Hu-UCB

-USSC

(ii)m

BM-M

SCUltraC

ULT

URE

medium

75

BABL

cserum

5CO

260

48ho

urs

NA

NA

[14]

Hu-BM

-MSC

120572MEM

10FB

S5

CO2

2times10

7 flask

60ndash70

Till60ndash70

P5Con

c50xmdash

5kD

5flaskrarr

100120583

L[22]

Hu-BM

-MSC

NA-

005BS

ANA

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[26]

Hu-BM

-MSC

DMEM

-005

BSA

norm

oxia

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[27]

Hu-BM

-MSC

DMEM

-005

BSA

5CO

205

O2

2times10

6rarr

split

12

rarrconfl

24ho

urs

P3ndash7

Con

c25x

3kD

[17]

Hu-BM

-MNC-

stro-3-MPC

120572MEM

NA

1times10

6MPC

NA

P5Con

c

[25]

(i)Hu-BM

-MSC

(ii)H

u-BM

-CD133

(iii)Hu-BM

-p75

(iv)H

u-fib

ro

120572MEM

5CO

2(i)

1O

2(ii)2

1O

2

1times10

6

90

48ho

urs

P4-5

02120583

mmdash80∘C

conc40xmdash5k

D

[28]

Rat-B

M-M

SCDMEM

T75flask

NA

90

48ho

urs

P2ndash4

Con

c40xmdash

10kD

10m

Lrarr

250120583



Table2Con

tinued

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[19]

RatB

M-M

SCDMEM

-005

BSA

10mL

NA

80ndash9

012

hours

P3-4

Con

c25x

3kD

[23]

(i)Hu-SC

-EDT

(ii)B

M-M

SC(Lon

za)

DMEM

5CO

24times10

548

hours

P3ndash5

3000

rpmmdash3m

inrarr

supernatant

[3]

Hu-AD-M

SCNA

Hypoxia

NA

NA

NA

Con

c-fre

ezed

ried

[24]

Hu-AD-M

SC120572MEM

70mL

Spheroid

1O

2mdash5

CO2

42times107

2days

NA

Centr

[6]

Hu-AD-SC

CRM120572MEM

CRMmdashhu

allo10

120572MEM

mdashFB

S10

1O

2mdash5

CO2

25ndash3times

105 mLmdash

24mLmdash

150c

mdish

2days

Upto

P5Centr

CRM120572MEM

CRMmdashhu

allo10

120572MEM

FBS10

Spheroid

1O

2mdash5

CO2

6ndash12times

105 mLmdash

30120583L

rarr70

mLflask

[1]

Hu-AD-SC

NA

NA

Reference[1314]

1times10

5rarr

80

24ho

urs

NA

Centr

300g

5minmdash220n

m

[5]

Hu-AD-SC

DMEM

F12

2O

25

CO2

4times10

572

hours

P4-5

Centr

300g

5rsquo022120583m3

kD

[23]

Hu-MSC

DMEM

-005

BSA

15mLmdash

175c

m2flask

NA

1times10

6

70ndash80

24ho

urs

NA

Con

c25x3k

D

[31]

Hu-MSC

(cellline)

DMEM

-10

FBS

5mL

5CO

270

48ho

urs

NA

10000

0gmdash

1hou

rrarr

supernatant

022120583m

[33]

Hu-MSC

(Lon

za)

DMEM

5CO

270

48ho

urs

P3ndash9

4∘Corminus80∘C

[32]

Mou

se-iP

SCNA

NA

NA

NA

NA

NA

Hu

humanE

SCembryonicste

mcell

ECend

othelialcellHUVEC

hum

anum

bilical

vein

endo

thelialcellEP

Cendo

thelialp

rogenitorcell

AF

amniotic

fluidS

Cste

mcell

MSC

mesenchym

alSC

HPL

hepatic

progenito

r-lik

ecell

ADadipo

setissuederiv

edP

Bperip

heralb

lood

MNC

mon

onuclear

cell

UC

umbilicalcordU

CBU

Cbloo

dmm

ouseB

Mb

onemarrow

MPC

mesenchym

alprogenito

rcell

fibrofibrob

last

EDT

exfoliateddecidu

oustoo

thiPS

Cindu

cedpluripotentS

CTC

tissue

cultu

reN

Anot

availableFB

Sfetalbovines

erum

allo

allo

genics

erum

BSA

bovines

erum

albu


mrarr

10nmrarr

100n

myield

ed10ndash220

nmversus

10ndash100

nm(lt1000

kD)v

ersus100ndash220

nm(gt1000

kD)FC

fibron

ectin

coatedP

passageP

Dpop

ulationdo

ublin

gCM

con

ditio

nedmediumcon

cconcentrated

centrcentrifugation










EGF





















Table 3 Continued



[10]







(concentration NA)


VEGF

HGF










90T75Conc 40x






hPDGF-AA Both ND

[6]


2 days 105Centr






Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References





















































Table 1 Continued






[20]


Male SD rat Hu-MSC


[21]



[22]




[23]




[24]





[25]




[26]



[27]





[29]


(ii) Mouse BM-MSC


[30]



[31]



[32]


Table 1 Continued


















cond

ition

celln

umberdu

ratio


gof

cond

ition

edmedium

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[7]

Hu-ES

C-EC

HUVEC

EBM2

NA

NA

5days

NA

NA

[13]

(i)Hu-ES

C-CD

133KD

R-EP

C(ii)H

u-UCB

-EPC

EGM-2

(Lon

za)mdash

15mL

150m

mcultu

redish

NA

80

48ho

urs

P5ndash8

Con

c50x

10kD

[16]

[29]

Hu-ES

C-MSC

Hu-ES

C-MSC

DMEM

mdashinsulin

transferrin

seleno

protein

FGF2P

DGF-AB

glutam

ineand120573-M

E

NA

NA

NA

NA

3days

3days

ge80

PD80

PDCon

c25x10kD

mdash220n

mrarr

05m

gmLprotein

[18]

Hu-ES

C-MSC

Chem

icallydefin

edmedium

NA

NA

3days

80PD

Con

c25x

10kD119886

[9]

Hu-AFSC

mdashCk

it(+)

120572MEM

Six-wellplate

5CO

215000

070

16ho

urs

NA

from

50000

0cellsmdash1m

LmdashCon

crarr

80120583L

[20]

1-Hu-AF-MSC

2-hu

-AF-MSC

-HPL

DMEM

05

FBS

25cm

2TC

flask

5CO

215times10

6

80

24ho

urs

P5ndash13

Con

c25x

3kD

[8]

(i)Hu-PB

-MNC-

EPC

(ii)H

UVEC

EBM2(Lon

za)1FB

S15

O

25

CONA

72ho

urs

NA

NA

[15]

PorcineP

B-MNC-

EPC

Exvivo

15(Lon

za)mdash

VEG

F1n

gmLmdash

FCplate

5CO

2From

30ndash4

0mL

PB48

hours

P0Centr

600g


[12]

Hu-UC-

MSC

M199

5CO

2NA

24ho

urs

P3Con

c-02120583

m

[10]

(i)Hu-UCB

-MNC-

SC(end

othelial+

MSC

)(ii)H

UVEC

EGM-2ndash15m

L150m

mcultu

redish

5CO

280

48ho

urs

P5ndash8

Con

c50xmdash

10kD

[11]

Hu-UCB

-CD34-EPC

M199basalm

edium

5CO

21times

106

24ho

urs

NA

Con

c

[30]

(i)Hu-UCB

-USSC

(ii)m

BM-M

SCUltraC

ULT

URE

medium

75

BABL

cserum

5CO

260

48ho

urs

NA

NA

[14]

Hu-BM

-MSC

120572MEM

10FB

S5

CO2

2times10

7 flask

60ndash70

Till60ndash70

P5Con

c50xmdash

5kD

5flaskrarr

100120583

L[22]

Hu-BM

-MSC

NA-

005BS

ANA

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[26]

Hu-BM

-MSC

DMEM

-005

BSA

norm

oxia

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[27]

Hu-BM

-MSC

DMEM

-005

BSA

5CO

205

O2

2times10

6rarr

split

12

rarrconfl

24ho

urs

P3ndash7

Con

c25x

3kD

[17]

Hu-BM

-MNC-

stro-3-MPC

120572MEM

NA

1times10

6MPC

NA

P5Con

c

[25]

(i)Hu-BM

-MSC

(ii)H

u-BM

-CD133

(iii)Hu-BM

-p75

(iv)H

u-fib

ro

120572MEM

5CO

2(i)

1O

2(ii)2

1O

2

1times10

6

90

48ho

urs

P4-5

02120583

mmdash80∘C

conc40xmdash5k

D

[28]

Rat-B

M-M

SCDMEM

T75flask

NA

90

48ho

urs

P2ndash4

Con

c40xmdash

10kD

10m

Lrarr

250120583



Table2Con

tinued

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[19]

RatB

M-M

SCDMEM

-005

BSA

10mL

NA

80ndash9

012

hours

P3-4

Con

c25x

3kD

[23]

(i)Hu-SC

-EDT

(ii)B

M-M

SC(Lon

za)

DMEM

5CO

24times10

548

hours

P3ndash5

3000

rpmmdash3m

inrarr

supernatant

[3]

Hu-AD-M

SCNA

Hypoxia

NA

NA

NA

Con

c-fre

ezed

ried

[24]

Hu-AD-M

SC120572MEM

70mL

Spheroid

1O

2mdash5

CO2

42times107

2days

NA

Centr

[6]

Hu-AD-SC

CRM120572MEM

CRMmdashhu

allo10

120572MEM

mdashFB

S10

1O

2mdash5

CO2

25ndash3times

105 mLmdash

24mLmdash

150c

mdish

2days

Upto

P5Centr

CRM120572MEM

CRMmdashhu

allo10

120572MEM

FBS10

Spheroid

1O

2mdash5

CO2

6ndash12times

105 mLmdash

30120583L

rarr70

mLflask

[1]

Hu-AD-SC

NA

NA

Reference[1314]

1times10

5rarr

80

24ho

urs

NA

Centr

300g

5minmdash220n

m

[5]

Hu-AD-SC

DMEM

F12

2O

25

CO2

4times10

572

hours

P4-5

Centr

300g

5rsquo022120583m3

kD

[23]

Hu-MSC

DMEM

-005

BSA

15mLmdash

175c

m2flask

NA

1times10

6

70ndash80

24ho

urs

NA

Con

c25x3k

D

[31]

Hu-MSC

(cellline)

DMEM

-10

FBS

5mL

5CO

270

48ho

urs

NA

10000

0gmdash

1hou

rrarr

supernatant

022120583m

[33]

Hu-MSC

(Lon

za)

DMEM

5CO

270

48ho

urs

P3ndash9

4∘Corminus80∘C

[32]

Mou

se-iP

SCNA

NA

NA

NA

NA

NA

Hu

humanE

SCembryonicste

mcell

ECend

othelialcellHUVEC

hum

anum

bilical

vein

endo

thelialcellEP

Cendo

thelialp

rogenitorcell

AF

amniotic

fluidS

Cste

mcell

MSC

mesenchym

alSC

HPL

hepatic

progenito

r-lik

ecell

ADadipo

setissuederiv

edP

Bperip

heralb

lood

MNC

mon

onuclear

cell

UC

umbilicalcordU

CBU

Cbloo

dmm

ouseB

Mb

onemarrow

MPC

mesenchym

alprogenito

rcell

fibrofibrob

last

EDT

exfoliateddecidu

oustoo

thiPS

Cindu

cedpluripotentS

CTC

tissue

cultu

reN

Anot

availableFB

Sfetalbovines

erum

allo

allo

genics

erum

BSA

bovines

erum

albu


mrarr

10nmrarr

100n

myield

ed10ndash220

nmversus

10ndash100

nm(lt1000

kD)v

ersus100ndash220

nm(gt1000

kD)FC

fibron

ectin

coatedP

passageP

Dpop

ulationdo

ublin

gCM

con

ditio

nedmediumcon

cconcentrated

centrcentrifugation










EGF





















Table 3 Continued



[10]







(concentration NA)


VEGF

HGF










90T75Conc 40x






hPDGF-AA Both ND

[6]


2 days 105Centr






Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References





















































Table 1 Continued


















cond

ition

celln

umberdu

ratio


gof

cond

ition

edmedium

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[7]

Hu-ES

C-EC

HUVEC

EBM2

NA

NA

5days

NA

NA

[13]

(i)Hu-ES

C-CD

133KD

R-EP

C(ii)H

u-UCB

-EPC

EGM-2

(Lon

za)mdash

15mL

150m

mcultu

redish

NA

80

48ho

urs

P5ndash8

Con

c50x

10kD

[16]

[29]

Hu-ES

C-MSC

Hu-ES

C-MSC

DMEM

mdashinsulin

transferrin

seleno

protein

FGF2P

DGF-AB

glutam

ineand120573-M

E

NA

NA

NA

NA

3days

3days

ge80

PD80

PDCon

c25x10kD

mdash220n

mrarr

05m

gmLprotein

[18]

Hu-ES

C-MSC

Chem

icallydefin

edmedium

NA

NA

3days

80PD

Con

c25x

10kD119886

[9]

Hu-AFSC

mdashCk

it(+)

120572MEM

Six-wellplate

5CO

215000

070

16ho

urs

NA

from

50000

0cellsmdash1m

LmdashCon

crarr

80120583L

[20]

1-Hu-AF-MSC

2-hu

-AF-MSC

-HPL

DMEM

05

FBS

25cm

2TC

flask

5CO

215times10

6

80

24ho

urs

P5ndash13

Con

c25x

3kD

[8]

(i)Hu-PB

-MNC-

EPC

(ii)H

UVEC

EBM2(Lon

za)1FB

S15

O

25

CONA

72ho

urs

NA

NA

[15]

PorcineP

B-MNC-

EPC

Exvivo

15(Lon

za)mdash

VEG

F1n

gmLmdash

FCplate

5CO

2From

30ndash4

0mL

PB48

hours

P0Centr

600g


[12]

Hu-UC-

MSC

M199

5CO

2NA

24ho

urs

P3Con

c-02120583

m

[10]

(i)Hu-UCB

-MNC-

SC(end

othelial+

MSC

)(ii)H

UVEC

EGM-2ndash15m

L150m

mcultu

redish

5CO

280

48ho

urs

P5ndash8

Con

c50xmdash

10kD

[11]

Hu-UCB

-CD34-EPC

M199basalm

edium

5CO

21times

106

24ho

urs

NA

Con

c

[30]

(i)Hu-UCB

-USSC

(ii)m

BM-M

SCUltraC

ULT

URE

medium

75

BABL

cserum

5CO

260

48ho

urs

NA

NA

[14]

Hu-BM

-MSC

120572MEM

10FB

S5

CO2

2times10

7 flask

60ndash70

Till60ndash70

P5Con

c50xmdash

5kD

5flaskrarr

100120583

L[22]

Hu-BM

-MSC

NA-

005BS

ANA

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[26]

Hu-BM

-MSC

DMEM

-005

BSA

norm

oxia

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[27]

Hu-BM

-MSC

DMEM

-005

BSA

5CO

205

O2

2times10

6rarr

split

12

rarrconfl

24ho

urs

P3ndash7

Con

c25x

3kD

[17]

Hu-BM

-MNC-

stro-3-MPC

120572MEM

NA

1times10

6MPC

NA

P5Con

c

[25]

(i)Hu-BM

-MSC

(ii)H

u-BM

-CD133

(iii)Hu-BM

-p75

(iv)H

u-fib

ro

120572MEM

5CO

2(i)

1O

2(ii)2

1O

2

1times10

6

90

48ho

urs

P4-5

02120583

mmdash80∘C

conc40xmdash5k

D

[28]

Rat-B

M-M

SCDMEM

T75flask

NA

90

48ho

urs

P2ndash4

Con

c40xmdash

10kD

10m

Lrarr

250120583



Table2Con

tinued

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[19]

RatB

M-M

SCDMEM

-005

BSA

10mL

NA

80ndash9

012

hours

P3-4

Con

c25x

3kD

[23]

(i)Hu-SC

-EDT

(ii)B

M-M

SC(Lon

za)

DMEM

5CO

24times10

548

hours

P3ndash5

3000

rpmmdash3m

inrarr

supernatant

[3]

Hu-AD-M

SCNA

Hypoxia

NA

NA

NA

Con

c-fre

ezed

ried

[24]

Hu-AD-M

SC120572MEM

70mL

Spheroid

1O

2mdash5

CO2

42times107

2days

NA

Centr

[6]

Hu-AD-SC

CRM120572MEM

CRMmdashhu

allo10

120572MEM

mdashFB

S10

1O

2mdash5

CO2

25ndash3times

105 mLmdash

24mLmdash

150c

mdish

2days

Upto

P5Centr

CRM120572MEM

CRMmdashhu

allo10

120572MEM

FBS10

Spheroid

1O

2mdash5

CO2

6ndash12times

105 mLmdash

30120583L

rarr70

mLflask

[1]

Hu-AD-SC

NA

NA

Reference[1314]

1times10

5rarr

80

24ho

urs

NA

Centr

300g

5minmdash220n

m

[5]

Hu-AD-SC

DMEM

F12

2O

25

CO2

4times10

572

hours

P4-5

Centr

300g

5rsquo022120583m3

kD

[23]

Hu-MSC

DMEM

-005

BSA

15mLmdash

175c

m2flask

NA

1times10

6

70ndash80

24ho

urs

NA

Con

c25x3k

D

[31]

Hu-MSC

(cellline)

DMEM

-10

FBS

5mL

5CO

270

48ho

urs

NA

10000

0gmdash

1hou

rrarr

supernatant

022120583m

[33]

Hu-MSC

(Lon

za)

DMEM

5CO

270

48ho

urs

P3ndash9

4∘Corminus80∘C

[32]

Mou

se-iP

SCNA

NA

NA

NA

NA

NA

Hu

humanE

SCembryonicste

mcell

ECend

othelialcellHUVEC

hum

anum

bilical

vein

endo

thelialcellEP

Cendo

thelialp

rogenitorcell

AF

amniotic

fluidS

Cste

mcell

MSC

mesenchym

alSC

HPL

hepatic

progenito

r-lik

ecell

ADadipo

setissuederiv

edP

Bperip

heralb

lood

MNC

mon

onuclear

cell

UC

umbilicalcordU

CBU

Cbloo

dmm

ouseB

Mb

onemarrow

MPC

mesenchym

alprogenito

rcell

fibrofibrob

last

EDT

exfoliateddecidu

oustoo

thiPS

Cindu

cedpluripotentS

CTC

tissue

cultu

reN

Anot

availableFB

Sfetalbovines

erum

allo

allo

genics

erum

BSA

bovines

erum

albu


mrarr

10nmrarr

100n

myield

ed10ndash220

nmversus

10ndash100

nm(lt1000

kD)v

ersus100ndash220

nm(gt1000

kD)FC

fibron

ectin

coatedP

passageP

Dpop

ulationdo

ublin

gCM

con

ditio

nedmediumcon

cconcentrated

centrcentrifugation










EGF





















Table 3 Continued



[10]







(concentration NA)


VEGF

HGF










90T75Conc 40x






hPDGF-AA Both ND

[6]


2 days 105Centr






Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References






















































cond

ition

celln

umberdu

ratio


gof

cond

ition

edmedium

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[7]

Hu-ES

C-EC

HUVEC

EBM2

NA

NA

5days

NA

NA

[13]

(i)Hu-ES

C-CD

133KD

R-EP

C(ii)H

u-UCB

-EPC

EGM-2

(Lon

za)mdash

15mL

150m

mcultu

redish

NA

80

48ho

urs

P5ndash8

Con

c50x

10kD

[16]

[29]

Hu-ES

C-MSC

Hu-ES

C-MSC

DMEM

mdashinsulin

transferrin

seleno

protein

FGF2P

DGF-AB

glutam

ineand120573-M

E

NA

NA

NA

NA

3days

3days

ge80

PD80

PDCon

c25x10kD

mdash220n

mrarr

05m

gmLprotein

[18]

Hu-ES

C-MSC

Chem

icallydefin

edmedium

NA

NA

3days

80PD

Con

c25x

10kD119886

[9]

Hu-AFSC

mdashCk

it(+)

120572MEM

Six-wellplate

5CO

215000

070

16ho

urs

NA

from

50000

0cellsmdash1m

LmdashCon

crarr

80120583L

[20]

1-Hu-AF-MSC

2-hu

-AF-MSC

-HPL

DMEM

05

FBS

25cm

2TC

flask

5CO

215times10

6

80

24ho

urs

P5ndash13

Con

c25x

3kD

[8]

(i)Hu-PB

-MNC-

EPC

(ii)H

UVEC

EBM2(Lon

za)1FB

S15

O

25

CONA

72ho

urs

NA

NA

[15]

PorcineP

B-MNC-

EPC

Exvivo

15(Lon

za)mdash

VEG

F1n

gmLmdash

FCplate

5CO

2From

30ndash4

0mL

PB48

hours

P0Centr

600g


[12]

Hu-UC-

MSC

M199

5CO

2NA

24ho

urs

P3Con

c-02120583

m

[10]

(i)Hu-UCB

-MNC-

SC(end

othelial+

MSC

)(ii)H

UVEC

EGM-2ndash15m

L150m

mcultu

redish

5CO

280

48ho

urs

P5ndash8

Con

c50xmdash

10kD

[11]

Hu-UCB

-CD34-EPC

M199basalm

edium

5CO

21times

106

24ho

urs

NA

Con

c

[30]

(i)Hu-UCB

-USSC

(ii)m

BM-M

SCUltraC

ULT

URE

medium

75

BABL

cserum

5CO

260

48ho

urs

NA

NA

[14]

Hu-BM

-MSC

120572MEM

10FB

S5

CO2

2times10

7 flask

60ndash70

Till60ndash70

P5Con

c50xmdash

5kD

5flaskrarr

100120583

L[22]

Hu-BM

-MSC

NA-

005BS

ANA

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[26]

Hu-BM

-MSC

DMEM

-005

BSA

norm

oxia

2times10

624

hours

P3ndash7

Con

c25xmdash

3kD

[27]

Hu-BM

-MSC

DMEM

-005

BSA

5CO

205

O2

2times10

6rarr

split

12

rarrconfl

24ho

urs

P3ndash7

Con

c25x

3kD

[17]

Hu-BM

-MNC-

stro-3-MPC

120572MEM

NA

1times10

6MPC

NA

P5Con

c

[25]

(i)Hu-BM

-MSC

(ii)H

u-BM

-CD133

(iii)Hu-BM

-p75

(iv)H

u-fib

ro

120572MEM

5CO

2(i)

1O

2(ii)2

1O

2

1times10

6

90

48ho

urs

P4-5

02120583

mmdash80∘C

conc40xmdash5k

D

[28]

Rat-B

M-M

SCDMEM

T75flask

NA

90

48ho

urs

P2ndash4

Con

c40xmdash

10kD

10m

Lrarr

250120583



Table2Con

tinued

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[19]

RatB

M-M

SCDMEM

-005

BSA

10mL

NA

80ndash9

012

hours

P3-4

Con

c25x

3kD

[23]

(i)Hu-SC

-EDT

(ii)B

M-M

SC(Lon

za)

DMEM

5CO

24times10

548

hours

P3ndash5

3000

rpmmdash3m

inrarr

supernatant

[3]

Hu-AD-M

SCNA

Hypoxia

NA

NA

NA

Con

c-fre

ezed

ried

[24]

Hu-AD-M

SC120572MEM

70mL

Spheroid

1O

2mdash5

CO2

42times107

2days

NA

Centr

[6]

Hu-AD-SC

CRM120572MEM

CRMmdashhu

allo10

120572MEM

mdashFB

S10

1O

2mdash5

CO2

25ndash3times

105 mLmdash

24mLmdash

150c

mdish

2days

Upto

P5Centr

CRM120572MEM

CRMmdashhu

allo10

120572MEM

FBS10

Spheroid

1O

2mdash5

CO2

6ndash12times

105 mLmdash

30120583L

rarr70

mLflask

[1]

Hu-AD-SC

NA

NA

Reference[1314]

1times10

5rarr

80

24ho

urs

NA

Centr

300g

5minmdash220n

m

[5]

Hu-AD-SC

DMEM

F12

2O

25

CO2

4times10

572

hours

P4-5

Centr

300g

5rsquo022120583m3

kD

[23]

Hu-MSC

DMEM

-005

BSA

15mLmdash

175c

m2flask

NA

1times10

6

70ndash80

24ho

urs

NA

Con

c25x3k

D

[31]

Hu-MSC

(cellline)

DMEM

-10

FBS

5mL

5CO

270

48ho

urs

NA

10000

0gmdash

1hou

rrarr

supernatant

022120583m

[33]

Hu-MSC

(Lon

za)

DMEM

5CO

270

48ho

urs

P3ndash9

4∘Corminus80∘C

[32]

Mou

se-iP

SCNA

NA

NA

NA

NA

NA

Hu

humanE

SCembryonicste

mcell

ECend

othelialcellHUVEC

hum

anum

bilical

vein

endo

thelialcellEP

Cendo

thelialp

rogenitorcell

AF

amniotic

fluidS

Cste

mcell

MSC

mesenchym

alSC

HPL

hepatic

progenito

r-lik

ecell

ADadipo

setissuederiv

edP

Bperip

heralb

lood

MNC

mon

onuclear

cell

UC

umbilicalcordU

CBU

Cbloo

dmm

ouseB

Mb

onemarrow

MPC

mesenchym

alprogenito

rcell

fibrofibrob

last

EDT

exfoliateddecidu

oustoo

thiPS

Cindu

cedpluripotentS

CTC

tissue

cultu

reN

Anot

availableFB

Sfetalbovines

erum

allo

allo

genics

erum

BSA

bovines

erum

albu


mrarr

10nmrarr

100n

myield

ed10ndash220

nmversus

10ndash100

nm(lt1000

kD)v

ersus100ndash220

nm(gt1000

kD)FC

fibron

ectin

coatedP

passageP

Dpop

ulationdo

ublin

gCM

con

ditio

nedmediumcon

cconcentrated

centrcentrifugation










EGF





















Table 3 Continued



[10]







(concentration NA)


VEGF

HGF










90T75Conc 40x






hPDGF-AA Both ND

[6]


2 days 105Centr






Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References





















































Table2Con

tinued

Reference

number

Cell

type

Mediumvessel

Cultu

recond

ition

Cell

number

Duration

Passage

CMprocessin

g

[19]

RatB

M-M

SCDMEM

-005

BSA

10mL

NA

80ndash9

012

hours

P3-4

Con

c25x

3kD

[23]

(i)Hu-SC

-EDT

(ii)B

M-M

SC(Lon

za)

DMEM

5CO

24times10

548

hours

P3ndash5

3000

rpmmdash3m

inrarr

supernatant

[3]

Hu-AD-M

SCNA

Hypoxia

NA

NA

NA

Con

c-fre

ezed

ried

[24]

Hu-AD-M

SC120572MEM

70mL

Spheroid

1O

2mdash5

CO2

42times107

2days

NA

Centr

[6]

Hu-AD-SC

CRM120572MEM

CRMmdashhu

allo10

120572MEM

mdashFB

S10

1O

2mdash5

CO2

25ndash3times

105 mLmdash

24mLmdash

150c

mdish

2days

Upto

P5Centr

CRM120572MEM

CRMmdashhu

allo10

120572MEM

FBS10

Spheroid

1O

2mdash5

CO2

6ndash12times

105 mLmdash

30120583L

rarr70

mLflask

[1]

Hu-AD-SC

NA

NA

Reference[1314]

1times10

5rarr

80

24ho

urs

NA

Centr

300g

5minmdash220n

m

[5]

Hu-AD-SC

DMEM

F12

2O

25

CO2

4times10

572

hours

P4-5

Centr

300g

5rsquo022120583m3

kD

[23]

Hu-MSC

DMEM

-005

BSA

15mLmdash

175c

m2flask

NA

1times10

6

70ndash80

24ho

urs

NA

Con

c25x3k

D

[31]

Hu-MSC

(cellline)

DMEM

-10

FBS

5mL

5CO

270

48ho

urs

NA

10000

0gmdash

1hou

rrarr

supernatant

022120583m

[33]

Hu-MSC

(Lon

za)

DMEM

5CO

270

48ho

urs

P3ndash9

4∘Corminus80∘C

[32]

Mou

se-iP

SCNA

NA

NA

NA

NA

NA

Hu

humanE

SCembryonicste

mcell

ECend

othelialcellHUVEC

hum

anum

bilical

vein

endo

thelialcellEP

Cendo

thelialp

rogenitorcell

AF

amniotic

fluidS

Cste

mcell

MSC

mesenchym

alSC

HPL

hepatic

progenito

r-lik

ecell

ADadipo

setissuederiv

edP

Bperip

heralb

lood

MNC

mon

onuclear

cell

UC

umbilicalcordU

CBU

Cbloo

dmm

ouseB

Mb

onemarrow

MPC

mesenchym

alprogenito

rcell

fibrofibrob

last

EDT

exfoliateddecidu

oustoo

thiPS

Cindu

cedpluripotentS

CTC

tissue

cultu

reN

Anot

availableFB

Sfetalbovines

erum

allo

allo

genics

erum

BSA

bovines

erum

albu


mrarr

10nmrarr

100n

myield

ed10ndash220

nmversus

10ndash100

nm(lt1000

kD)v

ersus100ndash220

nm(gt1000

kD)FC

fibron

ectin

coatedP

passageP

Dpop

ulationdo

ublin

gCM

con

ditio

nedmediumcon

cconcentrated

centrcentrifugation










EGF





















Table 3 Continued



[10]







(concentration NA)


VEGF

HGF










90T75Conc 40x






hPDGF-AA Both ND

[6]


2 days 105Centr






Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References





























































EGF





















Table 3 Continued



[10]







(concentration NA)


VEGF

HGF










90T75Conc 40x






hPDGF-AA Both ND

[6]


2 days 105Centr






Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References





















































Table 3 Continued



[10]







(concentration NA)


VEGF

HGF










90T75Conc 40x






hPDGF-AA Both ND

[6]


2 days 105Centr






Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References





















































Table 3 Continued






NA NA













Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References





















































Table4Celln

umbertoprod

uceC

Mpera

pplication

volumeandmod

eofd

eliveryof

vario

uscellsourcesfor

vario

uscond

ition

sand

theo

utcome

Reference

number

Con

ditio

ndisease

Species

Cellsou

rceo

fCM

Cultu

remediumculture

typemdashcond

ition

Cell

numberapplication

Volumea

ndmod

eof

delivery

Outcome

[6]

Hindlim

bisc

hemiamdashdirect

Femalea

thym

icmicemdash

20ndash25g

rHu-AD-SC

120572MEM

mdashFB

S10m

onolayermdashhypo

x1

12000

40120583Lmdash

IMmdash7x

Goo

dresult

CRMmdashHu

allo10sph

eroidmdash

hypo

x1

48000

Bette

rresult

120572MEM

mdashFB

S10sph

eroidmdash

hypo

x1

Bette

rresult

[9]

Hindlim

bisc

hemiamdash10

days

MaleN

OD-SCI

Dmicemdash

10ndash12weeks

Hu-AF-SC

ndashCkit

(+)

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

50000

080120583Lmdash

IMmdash4x

Goo

dresult

[11]

Fullthickn

ess

wou

ndmdash5m

mdirect

Diabetic

-immun

odef

micemdash

17ndash23g

Hu-UCB

-CD

34-EPC

M199basalm

edium

(minus)m

onolayermdashno

rmoxia

1times10

6100120583

Lmdashintradermal

injection

Goo

dresult

[14]

Wou

nd30ndash50m

m2

120ndash

140m

m2 mdash

48ho

urs

MaleN

OD-SCI

Dmicemdash

4-5w

eeks

Hu-BM

-MSC

120572MEM

mdash10

FBSmon

olayermdashno

rmoxia

1times10

8100120583

LmdashSC

mdashperip

hery

wou

ndGoo

dresult

[17]

MCI

48ho

urs

Nud

e-athymicratmdash

6ndash8weeks

Hu-BM

-MNC-

stro-3-MPC

120572MEM

mdash(minus)m

onolayermdash

norm

oxia

1times10

6250120583

LIntram

yocardial

Goo

dresult

[20]

CCl4injuredacute

hepatic

failu

remdash24

hours

SCID

-NOD

micemdash

6ndash8weeks

Hu-AF-MSC

DMEM

mdash05

FBSmon

olayermdashno

rmoxia

15times10

6200120583

Lmdashintrahepatic

(leftliver

lobe)

Goo

dresult

Hu-AF-MSC

-HPL

Bette

rresult

[21]

Fulm

inanth

epatic

failu

remdash24

hours

MaleS

Dratmdash

250ndash

300g

Hu-MSC

DMEM

mdash005bo

vine

serum

albu

minm

onolayermdash

norm

oxia

15times10

6900120583

Lpenilevein

Goo

dresult

Increasedsurvival

[22]

MaleS

Dratmdash

280ndash

370g

Hu-BM

-MSC

NAmdash

005

BSAm

onolayermdash

norm

oxia

2times10

6900120583

LCM

Penilevein

Goo

dresult

Increasedsurvival

[23]

Focalcerebral

ischemiamdash72

hours

MaleS

Dratmdash

350ndash

400g

Hu-ED

T-SC

DMEM

(minus)m

onolayermdashno

rmoxia

40000

010x10120583

Lmdashintranasal

(left-rig

ht)

EverydayD3-D15

Goo

dresult

BM-M

SC(Lon

za)

Goo

dresult

[24]

Ischem

icStrokemdash8days

MaleS

Dmou

semdash8

weeks

Hu-AD-M

SC120572MEM

mdash(minus)s

pheroidmdash

hypo

xia

150400

Infusio

n05120583

Lho

ur-7


Goo

dresult

SCID

severec

ombinedim

mun

odeficiencyN

ODnon

obesed

iabeticSDSprague-D

awleyHuhu

manA

Dadipo

setissueSC

stem

cellAFam

nioticflu

idU

CBumbilicalcord

bloo

dEP

Cendo

thelialprogenitor

cellBM

bon

emarrow

MSC

mesenchym

alSC

MNC

mon

onuclear

cellMPC

mesenchym

alprogenito

rcellHPL

hepaticprogenito

r-lik

ecellandED

Texfoliateddecidu

oustoo

th


Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References





















































Adipose tissue

Bone marrow

Amniotic fluid

Umbilical cord

MSCCM

EPCCM

PB

UCB


Myocardial infarct

Limb ischemia
















4 Conclusion




Acknowledgment


References






















































4 Conclusion




Acknowledgment


References




















































prospect of stem cell conditioned medium in regenerative ......endothelialgrowth,homing,and aa [6]...

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