About OMICS GroupAbout OMICS GroupAbout OMICS GroupAbout OMICS GroupOMICS Group is an amalgamation of Open Access publications and

worldwide international science conferences and events. Established in theyear 2007 with the sole aim of making the information on Sciences andtechnology ‘Open Access’, OMICS Group publishes 500 online openaccess scholarly journals in all aspects of Science, Engineering, Managementand Technology journals. OMICS Group has been instrumental in taking theknowledge on Science & technology to the doorsteps of ordinary men andwomen. Research Scholars, Students, Libraries, Educational Institutions,Research centers and the industry are main stakeholders that benefittedgreatly from this knowledge dissemination. OMICS Group also organizes500 International conferences annually across the globe, where knowledgetransfer takes place through debates, round table discussions, posterpresentations, workshops, symposia and exhibitions.

About OMICS International ConferencesAbout OMICS International ConferencesAbout OMICS International ConferencesAbout OMICS International Conferences

OMICS International is a pioneer and leading science event organizer,

which publishes around 500 open access journals and conducts over 500

Medical, Clinical, Engineering, Life Sciences, Pharma scientific

conferences all over the globe annually with the support of more than

1000 scientific associations and 30,000 editorial board members and 3.5

million followers to its credit.

OMICS Group has organized 500 conferences, workshops and national

symposiums across the major cities including San Francisco, Las Vegas,

San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago,

Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing,

Hyderabad, Bengaluru and Mumbai.

Intracellular development of cardiac stem cells as a strategic avenue to secure self-renewal, regeneration and maintenance ofthe mammalian myocardium

Intracellular development of cardiac stem cells as a strategic avenue to secure self-renewal, regeneration and maintenance ofthe mammalian myocardium

Galina Belostotskaya

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation

Galina Belostotskaya

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation

Modern conceptions of self-renewal and regeneration of mammalian myocardiumModern conceptions of self-renewal and regeneration of mammalian myocardium

(A) Nadal-Ginard, et al. The cardiac stem cell compartment is indispensable for myocardial cell homeostasis, repair and regeneration in the adult. Stem Cell Res. 2014;13(3 Pt B):615-30.

(B) Leri, et al. Origin of cardiomyocytes in the adult heart. Circ Res. 2015; 116:150-66

A

SMC CM EC

B

SMC CM EC

Immunocytochemical identification of resident cardiac stem cells (CSCs) inside the cardiac colonies, DIV 11Immunocytochemical identification of resident cardiac stem cells (CSCs) inside the cardiac colonies, DIV 11

New

bo

rn r

ats

Isl1+ и Sca+ (Alexa 405, blue), c-kit+ (FITC, green), actin (Rhodamine-Phalloidin, red)

25 µm25 µm50 µm

20 µm20 µm30 µm

Isl1+ c-kit+ Sca+

20-d

ay-o

ld r

ats

Contracting cardiomyocyte colony in the culture of newborn rat cardiaс cellsContracting cardiomyocyte colony in the culture of newborn rat cardiaс cells

Сontraction rate: 10 beats/min, DIV 11

25 µm

The colony of endothelial cells formed by Isl+ CSCs in the culture of cardiac cells of 40-day-old rat, DIV 42The colony of endothelial cells formed by Isl+ CSCs in the culture of cardiac cells of 40-day-old rat, DIV 42

25 µm

Nuclei

Isl CD105

Light microscopy Confocal microscopy

5 µm

CSC-clones detected in the cardiac cells suspension (ex vivo) of mammals of different ages CSC-clones detected in the cardiac cells suspension (ex vivo) of mammals of different ages

5 µmAdult mouse

Adult mouse

10 µmAdult mouse

5 µmAdult mouse

10 µm

c-kit+ α-actinin

Adult mouse5 µm

c-kit+ α-actinin

Adult mouse

15 µm

NucleiIsl+ α-actinin

10 µmAdult mouse

Nuclei Nuclei

c-kit α- Sarc actinNuclei

1-day-old rat

c-kit α- Sarc actinNuclei

1-day-old rat5 µm5 µm

c-kit α- Sarc actinNuclei

5 µm1-day-old rat

c-kit α- Sarc actinNuclei

5 µm

Old rat

40-day-old rat

Sca Actin

40-day-old rat

Sca Actin

15 µm

40-day-old rat

Sca Actin

20 µm

c-kit α-actininNuclei

1.5 –year-old rat

Nuclei

10 µm

c-kit+ α-actininNuclei

40-day-old rat25 µm

c-kit+ α-actininNuclei

45-y-old woman

The initial stages of resident CSCs development inside mature cardiomyocytes of different ages rats in primary culture with formation cell-in-cell structure (CICSs)

The initial stages of resident CSCs development inside mature cardiomyocytes of different ages rats in primary culture with formation cell-in-cell structure (CICSs)

40-day-old rat, DIV 610 µm

E c-kit Sarc actinnuclei

Sca Phalloidinnuclei

20-day-oldrat, DIV 1110 µm

Fc-kit Sarc actinnuclei

10 µm

Newborn rat, DIV 6

D

c-kitСard myos

Newborn rat, DIV 6

Anuclei

c-kitСard myos

10 µmNewborn rat, DIV 6

Bnuclei

c-kitСard myos

Newborn rat, DIV 6

Cnuclei

Proofs for intracellular CSCs location inside of cardiomyocytesProofs for intracellular CSCs location inside of cardiomyocytes

11-nb

Isl Card myosin

Actin cytoskeleton

Isl R-Phl

[[[[[[[

Newborn rat, DIV 205 µm

Newborn rat, DIV 6

A

D

CSC-CICSs of different ages rats in culture CSC-CICSs of different ages rats in culture

Isl α-actinin

40-day-old rat, DIV 85 µm

BAAA

5 µm

c-kit Sarc actin

Newborn rat, DIV 6

A C c-kit α-actinin

Newborn rat, DIV 205 µm

c-kit Sarc actin

Newborn rat, DIV 6

F

5 µm

Newborn rat, DIV 10

c-kit Sarc actinE

5 µm

c-kit Sarc actin

40-day-old rat, DIV 65 µm

D

Proofs for CSCs proliferation (Ki67pos) inside cardiomyocytes in ex vivo experiments. Proofs for CSCs proliferation (Ki67pos) inside cardiomyocytes in ex vivo experiments.

c-kit Ki67

c-kit+-CICSs in the suspension of freshly isolated cardiac cells of 40-day-old rats.

Optical tomography of cell-in-cell structures (CICSs) in in vitro and ex vivo experimentsOptical tomography of cell-in-cell structures (CICSs) in in vitro and ex vivo experiments

40-day-old rat, DIV 6 20-day-old rat, in suspension (ex vivo)

Isl1 α-Sarc actinc-kit α-Sarc actin

25 µmNewborn rat, DIV 19

Г

5 µm

Newborn rat, DIV 10

Е c-kit Sarc actin

А

10 µm40-day-old rat, DIV 21

7.5 µmNewborn rat, DIV 16

c-kit α-actininБ Isl α-actininВ

Newborn rat, DIV 2510 µm

Isl R-Phl

Newborn rat, DIV 16

Д

The rupture of CICS capsule and the release of transient amplifying cells from the CICSThe rupture of CICS capsule and the release of transient amplifying cells from the CICS

The rupture of CICS capsule and the release of transient amplifying cells from the CICSsThe rupture of CICS capsule and the release of transient amplifying cells from the CICSs

The rupture of CICS capsule in cultureThe rupture of CICS capsule in culture

10 µm

Newborn rat, DIV 14

nuclei

Isl Troponin

25 µmNewborn rat, DIV 19

Isl1 Troponin

Newborn rat, DIV 14

CICSs detected in the suspension of mammals cardiac cells (ex vivo)CICSs detected in the suspension of mammals cardiac cells (ex vivo)

5 µm

Sca α-actinin

Old rat

A

5 µmAdult mouse

Bnuclei

c-kit α-actinin

5 µm1-year–old cattle

Cnuclei

Sca α-actinin

CICSs detected in the suspension of human cardiac cells (ex vivo)CICSs detected in the suspension of human cardiac cells (ex vivo)

7.5 µm 5 µm 5 µm 5 µm 5 µm

5 µm 10 µm5 µm5 µm 5 µm

Hypothetical mechanism of mammalian myocardiumself-renewalHypothetical mechanism of mammalian myocardiumself-renewal

Isl1+

SC

Sca+SC

c-kit+SC

Sca+

Isl1+

c-kit+

SC

SC

SC

Population of CSCs

Division Differentiation

TACs

2

Isl1+

SC

Sca+SC

c-kit+SC

Penetration

of CSC into

CM

“Cell-in-cell

structure”

The release of

TACs

The rupture of

host cell

TACs

Выводы

1. Формирование зрелых кардиомиоцитов в миокарде млекопитающихпроисходит 2 путями: путем клонообразования и посредствомвнутриклеточного развития резидентных КСК внутри зрелых клетокмиокарда приблизительно c одинаковой частотой 1 клон и 1 CICS per100000 cardiac cells.

2. Клонообразование является самым быстрым и продуктивным способомвоспроизводства зрелых клеток, давая популяцию сокращающихсякардиомиоцитов уже через 10-13 дней.

3. Внутриклеточное развитие КСК также дает значительное количествотранзиторных клеток (около 200) из одного кардиопредшественника, нотребует большего времени: до 25-40 дней.

4. Нарушение метаболизма сердечной мышцы сдвигает равновесие в туили другую сторону.

5. При ишемии и инфаркте, сопровождающихся ацидозом и гипоксией,дифференцировка клеток в составе колоний подавляется, в то время какколичество CICSs возрастает в 10-15 раз. Мы предполагаем, что переходна внутриклеточное развитие объясняет бездействие КСК при остройпатологии.

6. В противоположность этому снижение нагрузки на сердечную мышцу вовремя невесомости способствует клонообразованию КСК, не влияя наколичество CICSs.

Спасибо за внимание!Спасибо за внимание!

Thanks' for your kind attention!!!!!!

22

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