Adult c-kitpos Cardiac Stem Cells Are Necessary and Sufficient for Functional Cardiac Regeneration and Repair

被引：488

作者：

Ellison, Georgina M. ^{[1
,2
,5
,6
]}

Vicinanza, Carla ^{[1
,2
]}

Smith, Andrew J. ^{[5
,6
]}

Aquila, Iolanda ^{[2
]}

Leone, Angelo ^{[2
]}

Waring, Cheryl D. ^{[1
]}

Henning, Beverley J. ^{[1
]}

Stirparo, Giuliano Giuseppe ^{[7
]}

Papait, Roberto ^{[7
,8
]}

Scarfo, Marzia ^{[9
]}

Agosti, Valter ^{[3
,4
]}

Viglietto, Giuseppe ^{[3
,4
,9
]}

Condorelli, Gianluigi ^{[7
,8
,10
]}

Indolfi, Ciro ^{[2
]}

Ottolenghi, Sergio ^{[11
]}

Torella, Daniele ^{[1
,2
]}

Nadal-Ginard, Bernardo ^{[1
,5
,6
]}

机构：

[1] Liverpool John Moores Univ, Stem Cell & Regenerat Biol Unit BioStem, Liverpool L3 3AF, Merseyside, England

[2] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Lab Mol & Cellular Cardiol, I-88100 Catanzaro, Italy

[3] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Mol Oncol Lab, I-88100 Catanzaro, Italy

[4] Magna Graecia Univ Catanzaro, CIS Genom & Mol Pathol, I-88100 Catanzaro, Italy

[5] Kings Coll London, Sch Biomed Sci, Ctr Human & Aerosp Physiol Sci, London SE1 1UL, England

[6] Kings Coll London, Ctr Stem Cells & Regenerat Med, London SE1 1UL, England

[7] Humanitas Clin & Res Ctr, I-20098 Rozzano Milan, Italy

[8] Natl Res Council Italy CNR, Inst Genet & Biomed Res, I-20098 Rozzano Milan, Italy

[9] IRGS Biogem, I-83031 Avellino, Italy

[10] Univ Milan, I-20098 Milan, Italy

[11] Univ Milano Bicocca, Dept Biotechnol & Biosci, I-20126 Milan, Italy

来源：

CELL | 2013年 / 154卷 / 04期

关键词：

PROGENITOR CELLS; SELF-RENEWAL; HEART; EXPRESSION; CARDIOMYOCYTES; DIFFERENTIATION; CARDIOMYOPATHY; MYOCARDIUM; PRECURSORS; INFARCTION;

D O I：

10.1016/j.cell.2013.07.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The epidemic of heart failure has stimulated interest in understanding cardiac regeneration. Evidence has been reported supporting regeneration via transplantation of multiple cell types, as well as replication of postmitotic cardiomyocytes. In addition, the adult myocardium harbors endogenous c-kit(pos) cardiac stem cells (eCSCs), whose relevance for regeneration is controversial. Here, using different rodent models of diffuse myocardial damage causing acute heart failure, we show that eCSCs restore cardiac function by regenerating lost cardiomyocytes. Ablation of the eCSC abolishes regeneration and functional recovery. The regenerative process is completely restored by replacing the ablated eCSCs with the progeny of one eCSC. eCSCs recovered from the host and recloned retain their regenerative potential in vivo and in vitro. After regeneration, selective suicide of these exogenous CSCs and their progeny abolishes regeneration, severely impairing ventricular performance. These data show that c-kit(pos) eCSCs are necessary and sufficient for the regeneration and repair of myocardial damage.

引用

页码：827 / 842

页数：16

共 38 条

[1]

Takotsubo Cardiomyopathy A New Form of Acute, Reversible Heart Failure [J].

Akashi, Yoshihiro J. ;

Goldstein, David S. ;

Barbaro, Giuseppe ;

Ueyama, Takashi .

CIRCULATION, 2008, 118 (25) :2754-2762

[2]

Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy [J].

Askari, AT ;

Unzek, S ;

Popovic, ZB ;

Goldman, CK ;

Forudi, F ;

Kiedrowski, M ;

Rovner, A ;

Ellis, SG ;

Thomas, JD ;

DiCorleto, PE ;

Topol, EJ ;

Penn, MS .

LANCET, 2003, 362 (9385) :697-703

[3]

Adult cardiac stem cells are multipotent and support myocardial regeneration [J].

Beltrami, AP ;

Barlucchi, L ;

Torella, D ;

Baker, M ;

Limana, F ;

Chimenti, S ;

Kasahara, H ;

Rota, M ;

Musso, E ;

Urbanek, K ;

Leri, A ;

Kajstura, J ;

Nadal-Ginard, B ;

Anversa, P .

CELL, 2003, 114 (06) :763-776

[4]

Evidence for Cardiomyocyte Renewal in Humans [J].

Bergmann, Olaf ;

Bhardwaj, Ratan D. ;

Bernard, Samuel ;

Zdunek, Sofia ;

Barnabe-Heider, Fanie ;

Walsh, Stuart ;

Zupicich, Joel ;

Alkass, Kanar ;

Buchholz, Bruce A. ;

Druid, Henrik ;

Jovinge, Stefan ;

Frisen, Jonas .

SCIENCE, 2009, 324 (5923) :98-102

[5]

Kit regulatory elements required for expression in developing hematopoietic and germ cell lineages [J].

Cairns, LA ;

Moroni, E ;

Levantini, E ;

Giorgetti, A ;

Klinger, FG ;

Tatangelo, L ;

Tiveron, C ;

De Felici, M ;

Dolci, S ;

Magli, MC ;

Giglioni, B ;

Ottolenghi, S .

BLOOD, 2003, 102 (12) :3954-3962

[6]

Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin [J].

Chong, James J. H. ;

Chandrakanthan, Vashe ;

Xaymardan, Munira ;

Asli, Naisana S. ;

Li, Joan ;

Ahmed, Ishtiaq ;

Heffernan, Corey ;

Menon, Mary K. ;

Scarlett, Christopher J. ;

Rashidianfar, Amirsalar ;

Biben, Christine ;

Zoellner, Hans ;

Colvin, Emily K. ;

Pimanda, John E. ;

Biankin, Andrew V. ;

Zhou, Bin ;

Pu, William T. ;

Prall, Owen W. J. ;

Harvey, Richard P. .

CELL STEM CELL, 2011, 9 (06) :527-540

[7]

Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches [J].

Czechowicz, Agnieszka ;

Kraft, Daniel ;

Weissman, Irving L. ;

Bhattacharya, Deepta .

SCIENCE, 2007, 318 (5854) :1296-1299

[8]

Myocardial CXCR4 Expression Is Required for Mesenchymal Stem Cell Mediated Repair Following Acute Myocardial Infarction [J].

Dong, Feng ;

Harvey, James ;

Finan, Amanda ;

Weber, Kristal ;

Agarwal, Udit ;

Penn, Marc S. .

CIRCULATION, 2012, 126 (03) :314-324

[9]

Myocyte death and renewal: Modern concepts of cardiac cellular homeostasis [J].

Ellison G.M. ;

Torella D. ;

Karakikes I. ;

Nadal-Ginard B. .

Nature Clinical Practice Cardiovascular Medicine, 2007, 4 (Suppl 1) :S52-S59

[10]

Acute β-adrenergic overload produces myocyte damage through calcium leakage from the ryanodine receptor 2 but spares cardiac stem cells [J].

Ellison, Georgina M. ;

Torella, Daniele ;

Karakikes, Ioannis ;

Purushothaman, Saranya ;

Curcio, Antonio ;

Gasparri, Cosimo ;

Indolfi, Ciro ;

Cable, N. Tim ;

Goldspink, David F. ;

Nadal-Ginard, Bernardo .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (15) :11397-11409

← 1 2 3 4 →