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Cardiac Regeneration pp 19–39Cite as

Progenitor Cells from the Adult Heart

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Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 4))

Abstract

The adult myocardium harbours a population of resident (endogenous) multipotent cardiac stem and progenitor cells (eCSCs). Manipulation of these cells in situ and ex vivo has opened new therapeutic avenues for anatomical and functional myocardial regeneration. However, recently the ability of the c-kitpos stem and progenitor cells to transdifferentiate into new cardiomyocytes has been disputed. Within an already highly controversial research field, these publications have caused significant confusion in their interpretation. Importantly, identifying, tracing and characterising stem and progenitor cells according to expression of a single surface receptor such as c-kit do not identify eCSCs. As discussed in this chapter, eCSCs isolated from the adult heart have a specific phenotype, being negative for blood lineage markers such as CD34, CD45 and CD31, and exhibit properties of stem and progenitor cells, being clonogenic, self-renewing and multipotent. Under the appropriate conditions, eCSCs differentiate into fully functional beating cardiomyocytes and regenerate cardiomyocytes lost from damage in vivo. Finally, eCSCs are susceptible to the effects of ageing, making regulation of this parameter highly impactful in the efficacy of myocardial regenerative therapies.

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References

  • Acosta JC, O'Loghlen A, Banito A et al (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133(6):1006–1018

    Article  CAS  PubMed  Google Scholar 

  • Angert D, Berretta RM, Kubo H et al (2011) Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells. Circ Res 108(10):1226–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antelmi I, de Paula RS, Shinzato AR et al (2004) Influence of age, gender, body mass index, and functional capacity on heart rate variability in a cohort of subjects without heart disease. Am J Cardiol 93(3):381–385

    Article  PubMed  Google Scholar 

  • Arsalan M, Woitek F, Adams V et al (2012) Distribution of cardiac stem cells in the human heart. ISRN Cardiol 2012:483407

    Article  PubMed  PubMed Central  Google Scholar 

  • Asakura A, Rudnicki MA (2002) Side population cells from diverse adult tissues are capable of in vitro hematopoietic differentiation. Exp Hematol 30(11):1339–1345

    Article  PubMed  Google Scholar 

  • Baker DJ, Wijshake T, Tchkonia T et al (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479:232–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barandon L, Couffinhal T, Ezan J et al (2003) Reduction of infarct size and prevention of cardiac rupture in transgenic mice overexpressing FrzA. Circulation 108(18):2282–2289

    Article  CAS  PubMed  Google Scholar 

  • Bearzi C, Rota M, Hosoda T et al (2007) Human cardiac stem cells. PNAS 104(35):14068–14073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beerman I, Maloney WJ, Weissmann IL et al (2010) Stem cells and the aging hematopoietic system. Curr Opin Immunol 22(4):500–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beltrami AP, Barlucchi L, Torella D et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776

    Article  CAS  PubMed  Google Scholar 

  • Beltrami AP, Cesselli D, Beltrami CA (2011) At the stem of youth and health. Pharmacol Ther 129(1):3–20

    Article  CAS  PubMed  Google Scholar 

  • Bergmann O, Bhardwaj RD, Bernard S et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergmann O, Zdunek S, Felker A et al (2015) Dynamics of cell generation and turnover in the human heart. Cell 161(7):1566–1575

    Article  CAS  PubMed  Google Scholar 

  • Bersell K, Arab S, Haring B et al (2009) Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell 138:257–270

    Article  CAS  PubMed  Google Scholar 

  • Boquoi A, Arora S, Chen T et al (2015) Reversible cell cycle inhibition and premature aging features imposed by conditional expression of p16Ink4a. Aging Cell 14(1):139–147

    Article  CAS  PubMed  Google Scholar 

  • Boström P, Mann N, Wu J et al (2010) C/EBPβ controls exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell 143:1072–1083

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120:513–522

    Article  CAS  PubMed  Google Scholar 

  • Cesselli D, Beltrami AP, D'Aurizio F et al (2011) Effects of age and heart failure on human cardiac stem cell function. Am J Pathol 179(1):349–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chien KR, Olson EN (2002) Converging pathways and principles in heart development and disease: CV@CSH. Cell 110:153–162

    Article  CAS  PubMed  Google Scholar 

  • Chimenti C, Kajstura J, Torella D et al (2003) Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res 93(7):604–613

    Article  CAS  PubMed  Google Scholar 

  • Chong JJ, Chandrakanthan V, Xaymardan M et al (2011) Adult cardiac-resident MSC-like stem cells with a proepicardial origin. Cell Stem Cell 9:527–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conboy IM, Conboy MJ, Wagers AJ et al (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764

    Article  CAS  PubMed  Google Scholar 

  • Coppé J, Desprez P, Krtolica A et al (2010) The Senescence-Associated Secretory Phenotype: the dark side of tumor suppression. Annu Rev Pathol 5:99–118

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • D'Amario D, Cabral-Da-Silva MC, Zheng H et al (2011) Insulin-like growth factor-1 receptor identifies a pool of human cardiac stem cells with superior therapeutic potential for myocardial regeneration. Circ Res 108(12):1467–1481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dawn B, Stein AB, Urbanek K et al (2005) Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. PNAS 102:3766–3771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Don CW, Murry CE (2013) Improving survival and efficacy of pluripotent stem cell-derived cardiac grafts. J Cell Mol Med 17(11):1355–1362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dutta D, Calvani R, Bernabei R et al (2012) Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities. Circ Res 110(8):1125–1138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ecob-Prince M, Hill M, Brown W (1989) Immunocytochemical demonstration of myosin heavy chain expression in human muscle. J Neurol Sci 91:71–78

    Article  CAS  PubMed  Google Scholar 

  • Eisenberg CA, Burch JB, Eisenberg LM (2006) Bone marrow cells transdifferentiate to cardiomyocytes when introduced into the embryonic heart. Stem Cells 24:1236–1245

    Article  CAS  PubMed  Google Scholar 

  • Ellison GM, Torella D, Karakikes I et al (2007a) Acute beta-adrenergic overload produces myocyte damage through calcium leakage from the ryanodine receptor 2 but spares cardiac stem cells. J Biol Chem 282:11397–11409

    Article  CAS  PubMed  Google Scholar 

  • Ellison GM, Torella D, Karakikes I et al (2007b) Myocyte death and renewal: modern concepts of cardiac cellular homeostasis. Nat Clin Pract Cardiovasc Med 4(Suppl 1):S52–S59

    Article  CAS  PubMed  Google Scholar 

  • Ellison GM, Galuppo V, Vicinanza C et al (2010) Cardiac stem and progenitor cell identification: different markers for the same cell? Front Biosci 2:641–652

    Google Scholar 

  • Ellison GM, Torella D, Dellegrottaglie S et al (2011) Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart. J Am Coll Cardiol 58(9):977–986

    Article  CAS  PubMed  Google Scholar 

  • Ellison GM, Nadal-Ginard B, Torella D (2012) Optimizing cardiac repair and regeneration through activation of the endogenous cardiac stem cell compartment. J Cardiovasc Transl Res 5(5):667–677

    Article  PubMed  Google Scholar 

  • Ellison GM, Vicinanza C, Smith AJ et al (2013) Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell 154(4):827–842

    Article  CAS  PubMed  Google Scholar 

  • Fang S, Wei J, Pentinmikko N et al (2012) Generation of functional blood vessels from a single c-kit+ adult vascular endothelial stem cell. PLoS Biol 10(10):e1001407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fazel S, Cimini M, Chen L et al (2006) Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 116(7):1865–1877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferreira-Martins J, Ogórek B, Cappetta D et al (2012) Cardiomyogenesis in the developing heart is regulated by c-kit-positive cardiac stem cells. Circ Res 110(5):701–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fischer KM, Cottage CT, Wu W et al (2009) Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase. Circulation 120(21):2077–2087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fleg JL, O'Connor F, Gerstenblith G et al (1995) Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol 78(3):890–900

    Article  CAS  PubMed  Google Scholar 

  • Flores I, Cayuela ML, Blasco MA (2005) Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309(5738):1253–1256

    Article  CAS  PubMed  Google Scholar 

  • Florian MC, Nattamai KJ, Dörr K (2013) A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing. Nature 503:392–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fransioli J, Bailey B, Gude NA et al (2008) Evolution of the c-kit-positive cell response to pathological challenge in the myocardium. Stem Cells 26(5):1315–1324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldspink DF, Burniston JG, Ellison GM et al (2004) Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo: the same or separate death pathways? Exp Physiol 89(4):407–416

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez A, Rota M, Nurzynska D et al (2008) Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circ Res 102(5):597–606

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Valdes I, Hidalgo I, Bujarrabal A et al (2015) Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence. Nat Commun 6:6473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goodell MA, Brose K, Paradis G et al (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183(4):1797–1806

    Article  CAS  PubMed  Google Scholar 

  • Hatzistergos KE, Takeuchi LM, Saur D et al (2015) cKit+ cardiac progenitors of neural crest origin. PNAS 112(42):13051–13056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hierlihy AM, Seale P, Lobe CG et al (2002) The post-natal heart contains a myocardial stem cell population. FEBS Lett 530(1–3):239–243

    Article  CAS  PubMed  Google Scholar 

  • Hsieh PC, Segers VF, Davis ME et al (2007) Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med 13(8):970–974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwakura T, Mohri T, Hamatani T et al (2011) STAT3/Pim-1 signaling pathway plays a crucial role in endothelial differentiation of cardiac resident Sca-1+ cells both in vitro and in vivo. J Mol Cell Cardiol 51(2):207–214

    Article  CAS  PubMed  Google Scholar 

  • Janzen V, Forkert R, Fleming HE et al (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443(7110):421–426

    Article  CAS  PubMed  Google Scholar 

  • Jesty SA, Steffey MA, Lee FK et al (2012) c-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart. PNAS 109(33):13380–13385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeyapalan JC, Sedivy JM (2008) Cellular senescence and organismal aging. Mech Ageing Dev 129(7–8):467–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kajstura J, Leri A, Finato N et al (1998) Myocyte proliferation in end-stage cardiac failure in humans. PNAS 95(15):8801–8805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kajstura J, Gurusamy N, Ogórek B et al (2010) Myocyte turnover in the aging human heart. Circ Res 107:1374–1386

    Article  CAS  PubMed  Google Scholar 

  • Kattman SJ, Huber TL, Keller GM (2006) Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Dev Cell 11:723–732

    Article  CAS  PubMed  Google Scholar 

  • Keith MC, Bolli R (2015) "String theory" of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results. Circ Res 116(7):1216–1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim WY, Sharpless NE (2006) The regulation of INK4/ARF in cancer and aging. Cell 127(2):265–275

    Article  CAS  PubMed  Google Scholar 

  • Krishnamurthy J, Torrice C, Ramsey MR et al (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114:1299–1307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kühn B, del Monte F, Hajjar RJ et al (2007) Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat Med 13:962–969

    Article  PubMed  CAS  Google Scholar 

  • Kuilman T, Peeper DS (2009) Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer 9(2):81–94

    Article  CAS  PubMed  Google Scholar 

  • Kuilman T, Michaloglou C, Mooi WJ et al (2010) The essence of senescence. Genes Dev 24(22):2463–2479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473:326–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lakatta EG, Levy D (2003a) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a "set up" for vascular disease. Circulation 107(1):139–146

    Article  PubMed  Google Scholar 

  • Lakatta EG, Levy D (2003b) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part II: the aging heart in health: links to heart disease. Circulation 107:346–354

    Article  PubMed  Google Scholar 

  • Laugwitz KL, Moretti A, Lam J et al (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433:647–653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lévesque JP, Hendy J, Winkler IG et al (2003) Granulocyte colony-stimulating factor induces the release in the bone marrow of proteases that cleave c-KIT receptor (CD117) from the surface of hematopoietic progenitor cells. Exp Hematol 31(2):109–117

    Article  PubMed  CAS  Google Scholar 

  • Li L, Clevers H (2010) Coexistence of quiescent and active adult stem cells in mammals. Science 327(5965):542–545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li TS, Cheng K, Malliaras K et al (2011) Expansion of human cardiac stem cells in physiological oxygen improves cell production efficiency and potency for myocardial repair. Cardiovasc Res 89(1):157–165

    Article  CAS  PubMed  Google Scholar 

  • Liang Y, Van Zant G, Szilvassy SJ (2005) Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 106(4):1479–1487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linke A, Müller P, Nurzynska D et al (2005) Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. PNAS 102(25):8966–8971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loffredo FS, Steinhauser ML, Gannon J et al (2011) Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell 8:389–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin K, Kirkwood TB, Potten CS (1998) Age changes in stem cells of murine small intestinal crypts. Exp Cell Res 241(2):316–323

    Article  CAS  PubMed  Google Scholar 

  • Martin CM, Meeson AP, Robertson SM et al (2004) Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol 265:262–275

    Article  CAS  PubMed  Google Scholar 

  • Matsuura K, Nagai T, Nishigaki N et al (2004) Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279:11384–11391

    Article  CAS  PubMed  Google Scholar 

  • Messina E, De Angelis L, Frati G et al (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95:911–921

    Article  CAS  PubMed  Google Scholar 

  • Miyamoto S, Kawaguchi N, Ellison GM et al (2010) Characterization of long-term cultured c-kit+ cardiac stem cells derived from adult rat hearts. Stem Cells Dev 19(1):105–116

    Article  CAS  PubMed  Google Scholar 

  • Mohsin S, Khan M, Toko H et al (2012) Human cardiac progenitor cells engineered with Pim-I kinase enhance myocardial repair. J Am Coll Cardiol 60(14):1278–1287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohsin S, Khan M, Nguyen J et al (2013) Rejuvenation of human cardiac progenitor cells with pim-1 kinase. Circ Res 113(10):1169–1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molofsky AV, Slutsky SG, Joseph NM et al (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moretti A, Caron L, Nakano A et al (2006) Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127:1151–1165

    Article  CAS  PubMed  Google Scholar 

  • Nadal-Ginard B (1978) Commitment, fusion and biochemical differentiation of a myogenic cell line in the absence of DNA synthesis. Cell 15:855–864

    Article  CAS  PubMed  Google Scholar 

  • Nadal-Ginard B, Kajstura J, Leri A et al (2003) Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92:139–150

    Article  CAS  PubMed  Google Scholar 

  • Nadal-Ginard B, Ellison GM, Torella D (2014) Absence of evidence is not evidence of absence: pitfalls of cre knock-ins in the c-Kit locus. Circ Res 115(4):415–418

    Article  CAS  PubMed  Google Scholar 

  • Nishimura EK, Granter SR, Fisher DE (2005) Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307(5710):720–724

    Article  CAS  PubMed  Google Scholar 

  • North BJ, Sinclair DA (2012) The intersection between aging and cardiovascular disease. Circ Res 110(8):1097–1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noseda M, Harada M, McSweeney S et al (2015) PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium. Nat Commun 6:6930

    Article  CAS  PubMed  Google Scholar 

  • Oh H, Bradfute SB, Gallardo TD et al (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. PNAS 100:12313–12318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Overy HR, Priest RE (1966) Mitotic cell division in postnatal cardiac growth. Lab Investig 15(6):1100–1103

    CAS  PubMed  Google Scholar 

  • Oyama T, Nagai T, Wada H et al (2007) Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo. J Cell Biol 176(3):329–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Passier R, van Laake LW, Mummery CL (2008) Stem-cell-based therapy and lessons from the heart. Nature 453(7193):322–329

    Article  CAS  PubMed  Google Scholar 

  • Passman JN, Dong XR, Wu SP et al (2008) A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells. PNAS 105(27):9349–9354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfister O, Mouquet F, Jain M et al (2005) CD31- but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ Res 97(1):52–61

    Article  CAS  PubMed  Google Scholar 

  • Potten CS, Loeffler M (1990) Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110(4):1001–1020

    Article  CAS  PubMed  Google Scholar 

  • Pouly J, Bruneval P, Mandet C et al (2008) Cardiac stem cells in the real world. J Thorac Cardiovasc Surg 135(3):673–678

    Article  PubMed  Google Scholar 

  • Quaini F, Urbanek K, Beltrami AP et al (2002) Chimerism of the transplanted heart. N Engl J Med 346:5–15

    Article  PubMed  Google Scholar 

  • Rasmussen TL, Raveendran G, Zhang J et al (2011) Getting to the heart of myocardial stem cells and cell therapy. Circulation 123:1771–1779

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodier F, Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192(4):547–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roskoski R Jr (2005) Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor. Biochem Biophys Res Commun 337(1):1–13

    Article  CAS  PubMed  Google Scholar 

  • Rossi DJ, Jamieson CH, Weissman IL (2008) Stems cells and the pathways to aging and cancer. Cell 132(4):681–696

    Article  CAS  PubMed  Google Scholar 

  • Rota M, LeCapitaine N, Hosoda T et al (2006) Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circ Res 99(1):42–52

    Article  CAS  PubMed  Google Scholar 

  • Samse K, Emathinger J, Hariharan N (2015) Functional effect of Pim1 depends upon intracellular localization in human cardiac progenitor cells. J Biol Chem 290(22):13935–13947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulman SP, Lakatta EG, Fleg JL (1992) Age-related decline in left ventricular filling at rest and exercise. Am J Phys 263(6 Pt 2):H1932–H1938

    CAS  Google Scholar 

  • Senyo SE, Steinhauser ML, Pizzimenti CL et al (2013) Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493(7432):433–436

    Article  CAS  PubMed  Google Scholar 

  • Sharpless NE, DePinho RA (2007) How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8(9):703–713

    Article  CAS  PubMed  Google Scholar 

  • Siddiqi S, Sussman MA (2013) Cardiac Hegemony of Senescence. Curr Transl Geriatr Exp Gerontol Rep 2(4):247–254

    Article  Google Scholar 

  • Smart N, Bollini S, Dubé KN et al (2011) De novo cardiomyocytes from within the activated adult heart after injury. Nature 474:640–644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith AJ, Lewis FC, Aquila I (2014) Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart. Nat Protoc 9(7):1662–1681

    Article  CAS  PubMed  Google Scholar 

  • Sousa-Victor P, Gutarra S, García-Prat L et al (2014) Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 506:316–321

    Article  CAS  PubMed  Google Scholar 

  • Sultana N, Zhang L, Yan J et al (2015) Resident c-kit(+) cells in the heart are not cardiac stem cells. Nat Commun 6:8701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takamiya M, Haider KH, Ashraf M (2011) Identification and characterization of a novel multipotent sub-population of Sca-1+ cardiac progenitor cells for myocardial regeneration. PLoS One 6(9):e25265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tallini YN, Greene KS, Craven M et al (2009) c-kit expression identifies cardiovascular precursors in the neonatal heart. PNAS 106(6):1808–1813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tchkonia T, Zhu Y, van Deursen J et al (2013) Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 123(3):966–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thijssen DH, Bullens LM, van Bemmel MM et al (2009) Does arterial shear explain the magnitude of flow-mediated dilation?: a comparison between young and older humans. Am J Physiol Heart Circ Physiol 296(1):H57–H64

    Article  CAS  PubMed  Google Scholar 

  • Torella D, Rota M, Nurzynska D et al (2004) Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res 94:514–524

    Article  CAS  PubMed  Google Scholar 

  • Torella D, Ellison GM, Méndez-Ferrer S et al (2006) Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S8–13

    Article  CAS  PubMed  Google Scholar 

  • Torella D, Ellison GM, Karakikes I et al (2007) Resident cardiac stem cells. Cell Mol Life Sci 64:661–673

    Article  CAS  PubMed  Google Scholar 

  • Urbanek K, Quaini F, Tasca G et al (2003) Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. PNAS 100:10440–10445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urbanek K, Torella D, Sheikh F et al (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. PNAS 102(24):8692–8697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Berlo JH, Molkentin JD (2014) An emerging consensus on cardiac regeneration. Nat Med 20(12):1386–1393

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van Berlo JH, Kanisicak O, Maillet M et al (2014) c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature 509(7500):337–341

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang X, Hu Q, Nakamura Y et al (2006) The role of the sca-1+/CD31–cardiac progenitor cell population in postinfarction left ventricular remodeling. Stem Cells 24(7):1779–1788

    Article  PubMed  Google Scholar 

  • Waring CD, Vicinanza C, Papalamprou A et al (2014) The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. Eur Heart J 35:2722–2731

    Article  CAS  PubMed  Google Scholar 

  • Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100(1):157–168

    Article  CAS  PubMed  Google Scholar 

  • Williams P, Simpson H, Kenwright J, Goldspink G (2001) Muscle fibre damage and regeneration resulting from surgical limb distraction. Cells Tissues Organs 169:395–400

    Article  CAS  PubMed  Google Scholar 

  • Wu SM, Fujiwara Y, Cibulsky SM et al (2006) Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell 127:1137–1150

    Article  CAS  PubMed  Google Scholar 

  • Xu M, Tchkonia T, Ding H, Ogrodnik M, Lubbers ER, Pirtskhalava T, White TA, Johnson KO, Stout MB, Mezera V, Giorgadze N, Jensen MD, LeBrasseur NK, Kirkland JL (2015a) JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc Natl Acad Sci U S A 112:E6301–E6310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu M, Palmer AK, Ding H, Weivoda MM, Pirtskhalava T, White TA, Sepe A, Johnson KO, Stout MB, Giorgadze N, Jensen MD, LeBrasseur NK, Tchkonia T, Kirkland JL (2015b) Targeting senescent cells enhances adipogenesis and metabolic function in old age. elife 4:pii: e12997

    Article  Google Scholar 

  • Yang MJ, Chen CH, Lin PJ et al (2007) Novel method of forming human embryoid bodies in a polystyrene dish surface-coated with a temperature-responsive methylcellulose hydrogel. Biomacromolecules 8(9):2746–2752

    Article  CAS  PubMed  Google Scholar 

  • Ye J, Boyle A, Shih H et al (2012) Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury. PLoS One 7(1):e30329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaruba MM, Soonpaa M, Reuter S et al (2010) Cardiomyogenic potential of C-kit(+)-expressing cells derived from neonatal and adult mouse hearts. Circulation 121(18):1992–2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou S, Schuetz JD, Bunting KD et al (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7(9):1028–1034

    Article  CAS  PubMed  Google Scholar 

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Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All experimental procedures were performed in accordance with the British Home Office Animals (Scientific Procedures) Act 1986 by appropriately qualified staff and approved by the institutional animal welfare and ethical review board.

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Authors and Affiliations

  1. Centre of Human and Aerospace Physiological Sciences and Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences and Medicine, King’s College London, London, SE1 1UL, UK

    Georgina M. Ellison-Hughes & Fiona C. Lewis

Authors
  1. Georgina M. Ellison-Hughes
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  2. Fiona C. Lewis
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Correspondence to Georgina M. Ellison-Hughes .

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Editors and Affiliations

  1. Keio University, School of Medicine, Department of Cardiology, Tokyo, Japan

    Masaki Ieda

  2. Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University, Göttingen, Germany

    Wolfram-Hubertus Zimmermann

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Ellison-Hughes, G.M., Lewis, F.C. (2017). Progenitor Cells from the Adult Heart. In: Ieda, M., Zimmermann, WH. (eds) Cardiac Regeneration. Cardiac and Vascular Biology, vol 4. Springer, Cham. https://doi.org/10.1007/978-3-319-56106-6_2

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