11. stem cell and regenerative medicine

8/10/2019 11. Stem Cell and Regenerative Medicine

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Stem cell and

Regenerative Medicine

Kiagus M Arsyad

Bagian Biologi Kedokteran

Fakultas Kedokteran UNSRI



LEARNING OBJECTIVES

At the end of this lecture student

should be able to know and

understand to :1. Stem cell and its types.

2. the sources of stem cell,

3. regenerative medicine and itsrelation to stem cell and application in

medicine and health



LEARNING CONTENTS

1. Stem cell

2. Application of stem cell

3. Regenerative Medicine

4. Development of Regenerative

Medicine

5. Conclusion



1. Stem cell

Stem cells are primal cells common to

all multi-cellular organisms that retain the

ability to renew themselves through cell

division and can differentiate into a widerange of specialized cell types.

The human stem cell field research

findings by Canadian scientists Ernest A.McCulloch and James E. Till in the

1960s.



1. Stem cell

In a developing embryo,

stem cells are able to differentiate into

all of the specialized embryonictissues.

In adult organisms,

stem cells and progenitor cells act asa repair system for the body,

replenishing specialized cells.



1. Stem cell

As stem cells can be readily grown

and transformed into specialised cells

with characteristics consistent withcells of various tissues such as

muscles or nerves through cell

culture, their use in medical therapies

has been proposed.



1. Stem cell

In particular, embryonic cell lines,

autologous embryonic stem cells

generated through therapeutic cloning,and highly plastic adult stem cells from

the umbilical cord blood or bone marrow

are touted as promising candidates.



Pluripotent, embryonic stem cells originate as inner mass cells with in a

blastocyst. The stem cells can become any tissue in the body, excluding

a placenta. Only the morula's cells are totipotent, able to become all

tissues and a placenta.



Pluripotent, embryonic stem cells originate as inner mass cells with in a

blastocyst. The stem cells can become any tissue in the body, excluding a

placenta. Only the morula's cells are totipotent, able to become all tissues

and a placenta.

morula



1. Stem cell

Totipotent stem cells can differentiate

into any cell type in the body plus the

placenta, which nourishes the embryo. A fertilized egg is a type of totipotent

stem cell.

Cells produced in the first few

divisions of the fertilized egg are also

totipotent.



1. Stem cell

Pluripotent stem cells are

descendants of the totipotent stem

cells of the embryo. These cells, which develop about four

days after fertilization, can

differentiate into any cell type, except

for totipotent stem cells and the cellsof the placenta.



1. Stem cell

Multipotent stem cells are descendents of

pluripotent stem cells and antecedents of

specialized cells in particular tissues, ex. :

Hematopoietic stem cells, which are found

primarily in the bone marrow, give rise to all of

the cells found in the blood, including red blood

cells, white blood cells, and platelets.

neural stem cells, which can differentiate intonerve cells and neural support cells called glia.



1.Stem cell

Progenitor cells (or unipotent stem

cells) can produce only one cell type.

For example, erythroid progenitor cellsdifferentiate into only red blood cells.



Stem cell division and

differentiation.

A - stem cell;

B - progenitor cell;

C - differentiated cell;

1 - symmetric stem

cell division; 2 - asymmetric stem

cell division;

3 - progenitor division;

4 - terminaldifferentiation



1. Stem cell

The three broad categories of

mammalian stem cells exist:

1. embryonic stem cells , derived fromblastocysts,

2. adul t stem cel ls , which are found in

adult tissues,

3. co rd blood s tem cel ls , which are

found in the umbilical cord.



Types of Human Stem Cells

Human

EmbryonicStem Cells

(hESC)

HumanAdult

Stem Cells(hASC)

Occur only inearlydevelopment

Occur in adultorganisms

Cord bloodstem cel)

Found inUmbilical cord



How to collect SC ?



Blood stem cells (Hematopoietics) taken from an umbilical cord.



1.1. Embryonic stem cells

(ESCs)

Derived from 4- to 5-day-old embryos are

known as blastocysts spherical

Each blastocyst consists of 50 to 150 cells

and includes three structures:

1. an outer layer of cells,

2. a fluid-filled cavity, and

3. a group of about 30 pluripotent cells at oneend of the cavity called the inner cell mass,

form all the cells of the body.



Embryonic vs adult stem cells

ES cells are pluripotent AS cells found in small amounts throughout body

Most AS cells appear to be multipotent

ES cells come from ICM of blastocyst

Reproduced by permission of the NIH



Sources of ES cells

1. ES cell lines

2. Excess embryos from IVF (in vitro fertilization)

clinics

3. Embryos created for research by IVF

4. Therapeutic cloning

Reproduced by permission of the NIH



Blastocyst -from In Vitro Fertilization Clinic

Inner Cell Mass

(Stem Cells)

“Blueprint” cells

A primer on Human Embryonic Stem Cells

A Blastocyst is a hollow ball of cellswith a small clump of stem cells inside



“Blueprint”

cells

Human Embryonic Stem Cells

Pipette

Stem Cells

To remove the stem cells, the Blastocyst is openedand the stem cells removed with a pipette


Stem Cells “Blueprint” cells

A Blastocyst is a hollow ball of cells with a

small clump of stem cells inside



Pipette

Pipette

Stem Cells

Petri Dish

Human Embryonic Stem Cells

To remove the stem cells, the Blastocyst is

broken open and the stem cells removed with

a pipette(an ultra thin glass tube)

The stem cells areplaced in a

dish and are fed andcared for

(each blastocyst =1 stem cell line)


Stem Cells “Blueprint” cells

A Blastocyst is a hollow ball of cells with a

small clump of stem cells inside

Stem Cells

“Blueprint”

cells



Neuron

Muscle

cell

PancreaticIslet

Petri DishStem Cells

Different chemicals / molecules are added to the stem

cells to make them become specific types of cells.

Growth factors Chemical cues



Donor Egg Skin Cell

Needle

Nucleus

(DNA) Nucleus

(DNA)

Needle

Chemicals and

Growth Factors

Dividing cells

Neuron

Muscle cell

PancreaticIslet

Stem Cells

Somatic Cell Nuclear Transfer or Therapeutic Cloning

BlastocystStem Cells



Blastocyst -

Stem Cells

Pipette

Stem Cells

“Blueprint” cells

Stem

Cells

Petri Dish

“Blueprint”

cells

To make stem cells into nerve cells

The stem cells are treated with

factors to cause them to differentiate

into particular cell types Stem cells differentiated into neurons



2. Application of The stem

cell Why all the fuss?

Stem cells may be able

to replace damaged

cells in the body

Today: lymphoma,leukemia

Future? Parkinson’s,

Alzheimer’s, diabetes...

Promising animal

studies

Reproduced by permission of The Providence Journal

Courtesy of The Michael J. Fox Foundation for Parkinson’s

Research



Ethical debate

Harvesting ES cells

destroys the

blastocyst

“This is murder”

Reproduced by permission of Dave Catrow and Copley News

Service



Ethical debate, cont’d

ES cell research

requires human cells

Could create a

commercial market for

human cells

“This devalues life”

Courtesy of Kevin Siers, The Charlotte Observer © 2001



Ethical debate, cont’d

“If excess IVF

embryos are

being discarded

anyway, theyshould be put to

good use”

Reprinted by permission of Chip Bok and Creators Syndicate, Inc.



3. REGENERATIVE MEDICINE

Definition

Regenerative medicine is the

"process of replacing or regeneratinghuman cells, tissues or organs to

restore or establish normal function"1.




This field holds the promise ofregenerating damaged tissues andorgans in the body by replacing

damaged tissue and/or by stimulatingthe body's own repair mechanisms toheal previously irreparable tissues ororgans.




Regenerative medicine also empowersscientists to grow tissues and organs in thelaboratory and safely implant them when thebody cannot heal itself.

Importantly, regenerative medicine has thepotential to solve the problem of the shortage oforgans available for donation compared to thenumber of patients that require life-saving organ

transplantation, as well as solve the problem oforgan transplant rejection, since the organ'scells will match that of the patient.

http://en.wikipedia.org/wiki/Organ_transplant

http://en.wikipedia.org/wiki/Organ_transplant



3.REGENERATIVE MEDICINE

first been coined by William Haseltine (founder ofHuman Genome Sciences).

From the work of Michael Lysaght (BrownUniversity), his team "first found the term in a 1992

article on hospital administration by Leland Kaiser.Kaiser’s paper closes with a series of short paragraphs on future technologies that will impacthospitals. One such paragraph had ‘‘RegenerativeMedicine’’ as a bold print title and went on to state,

‘‘A new branch of medicine will develop thatattempts to change the course of chronic diseaseand in many instances will regenerate tired andfailing organ systems.’’

http://en.wikipedia.org/wiki/Human_Genome_Sciences

http://en.wikipedia.org/wiki/Human_Genome_Sciences




Regenerative Medicine refers to a group ofbiomedical approaches to clinical therapies thatmay involve the use of stem cel ls . Examplesinclude;

1. the injection of stem cells or progenitor cells (cel l therapies );

2. another the induction of regeneration bybiologically active molecules administered

alone or as a secretion by infused cells( immunom odulat ion therapy );

3. and a third is transplantation of in vitro grownorgans and tissues (Tissue eng ineer ing).

http://en.wikipedia.org/wiki/Stem_cell

http://en.wikipedia.org/wiki/Progenitor_cell

http://en.wikipedia.org/wiki/Regeneration_(biology)

http://en.wikipedia.org/wiki/Organ_transplantation

http://en.wikipedia.org/wiki/Organ_transplantation

http://en.wikipedia.org/wiki/Regeneration_(biology)

http://en.wikipedia.org/wiki/Progenitor_cell

http://en.wikipedia.org/wiki/Stem_cell



4. DEVELOPMENT IN

REGENERATIVE MEDICINE

At the Wake Forest Institute for Regenerative Medicine, inNorth Carolina, Dr. Anthony Atala and his colleagues havesuccessfully extracted muscle and bladder cells fromseveral patients' bodies, cultivated these cells in petri

dishes, and then layered the cells in three-dimensionalmolds that resembled the shapes of the bladders. Withinweeks, the cells in the molds began functioning as regularbladders which were then implanted back into the patients'bodies.The team is currently working on re-growing over 22

other different organs including the Liver, Heart, Kidneysand Testicles.

http://en.wikipedia.org/wiki/Wake_Forest_Institute_for_Regenerative_Medicine

http://en.wikipedia.org/wiki/Anthony_Atala

http://en.wikipedia.org/wiki/Anthony_Atala

http://en.wikipedia.org/wiki/Wake_Forest_Institute_for_Regenerative_Medicine



4. THE DEVELOPMENT IN


Dr. Stephen Badylak, a Research Professor in the Department of Surgeryand director of Tissue Engineering at the McGowan Institute for RegenerativeMedicine at the University of Pittsburgh, has developed a process whichinvolves scraping cells from the lining of a pig's bladder , decellularizing

(removing cells to leave a clean extracellular structure) the tissue and thendrying it to become a sheet or a powder.

This cellular matrix powder was used to regrow the finger of Lee Spievak,who had severed half an inch of his finger after getting it caught in a propellerof a model plane.

However, Ben Goldacre has described this as "the missing finger that neverwas", claiming that fingertips regrow and quoted Simon Kay, professor of

hand surgery at the University of Leeds, who from the picture provided byGoldacre described the case as seemingly "an ordinary fingertip injury withquite unremarkable healing" and as "junk science".

I

http://en.wikipedia.org/w/index.php?title=Stephen_Badylak&action=edit&redlink=1

http://en.wikipedia.org/wiki/University_of_Pittsburgh

http://en.wikipedia.org/wiki/Pig%27s_bladder


http://en.wikipedia.org/wiki/Ben_Goldacre

http://en.wikipedia.org/wiki/Ben_Goldacre


http://en.wikipedia.org/wiki/University_of_Pittsburgh

http://en.wikipedia.org/w/index.php?title=Stephen_Badylak&action=edit&redlink=1



4. THE DEVELOPMENT IN


In June 2008, at the Hospital Clínic de Barcelona, Professor PaoloMacchiarini and his team, of the University of Barcelona,performed the first tissue engineered trachea (wind pipe)transplantation.

Adult stem cells were extracted from the patient's bone marrow,grown into a large population, and matured into cartilage cells, orchondrocytes, using an adaptive method originally devised fortreating osteoarthritis. The team then seeded the newly grownchondrocytes, as well as epithileal cells, into a decellularised (freeof donor cells) tracheal segment that was donated from a 51 year

old transplant donor who had died of cerebral hemorrhage. Afterfour days of seeding, the graft was used to replace the patient's leftmain bronchus. After one month, a biopsy elicited local bleeding,indicating that the blood vessels had already grown backsuccessfully.

http://en.wikipedia.org/wiki/Hospital_Cl%C3%ADnic

http://en.wikipedia.org/wiki/Paolo_Macchiarini


http://en.wikipedia.org/wiki/University_of_Barcelona

http://en.wikipedia.org/wiki/Chondrocyte

http://en.wikipedia.org/wiki/Chondrocyte

http://en.wikipedia.org/wiki/University_of_Barcelona



http://en.wikipedia.org/wiki/Hospital_Cl%C3%ADnic



Therapeutic cloning



Conclusion

By biomolecular, stem cell and cloning

biotechnologies regenerative medicine as new

field in medicine could be developed as treatment

for repair, change and substitute cells, tissues andorgan/(s) damage,

By induced Pluripotent cell an ethical aspect to

use ESC could be solved

Auto/Homolog-self treatment could be available



Stem Cell Banking

1. Cord Blood banking is now becoming popularfor autologous as well as for allogeneic donor

2. Adult Peripheral Blood collection andcryopreservation can also be used for future

diseases3. Stem cells can be collected from UCB and

Peripheral Blood by Apheresis

4. Stem cells can be Cryopreserved for use inCancers, CAD, Stroke, Diabetes, Burns, Spinal

Cord injury, Osteoarthritis, Regenerativemedicine, etc.

11. stem cell and regenerative medicine

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