Abstract
The common prevalence of heart failure and limitations in its treatment are leading cause of attention and interest towards the induction of cardiac regeneration with novel approaches. Recent studies provide growing evidence regarding bona fide cardiac regeneration post genetic manipulations, administration of stimulatory factors and myocardial injuries in animal models and human studies. To this end, stem cells of different sources have been tested to treat heart failure for the development of cellular therapies. Endogenous and exogenous stem cells sources used in regenerative cardiology have provided a proof of concept and applicability of cellular therapies in myocardial improvement. Recent clinical studies, especially, based on the endogenous cardiac progenitor and stem cells highlighted the possibility to regenerate lost cardiomyocytes in the myocardium. This review discusses emerging concepts in cardiac stem cell therapy, their sources and route of administration, and plausibility of de novo cardiomyocyte formation.
Semih Arbatlı and Galip Servet Aslan contributed equally to this work.
References
Anversa P, Kajstura J, Leri A, Bolli R (2006) Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation 113(11):1451–1463
Aslan GS, Mısır DG, Kocabas F (2015) Underlying mechanisms and prospects of heart regeneration. Turk J Biol 40:276. https://doi.org/10.3906/biy-1506-14
Bailey B, Fransioli J, Gude NA, Alvarez R Jr, Zhang X, Gustafsson AB, Sussman MA (2012) Sca-1 knockout impairs myocardial and cardiac progenitor cell function. Circ Res 111(6):750–760
Barile L, Chimenti I, Gaetani R, Forte E, Miraldi F, Frati G, Messina E, Giacomello A (2007) Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration. Nat Clin Pract Cardiovasc Med 4(Suppl 1):S9–S14
Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A, Yasuzawa-Amano S, Trofimova I, Siggins RW, Lecapitaine N, Cascapera S, Beltrami AP, D’Alessandro DA, Zias E, Quaini F, Urbanek K, Michler RE, Bolli R, Kajstura J, Leri A, Anversa P (2007) Human cardiac stem cells. Proc Natl Acad Sci U S A 104(35):14068–14073
Bearzi C, Leri A, Lo Monaco F, Rota M, Gonzalez A, Hosoda T, Pepe M, Qanud K, Ojaimi C, Bardelli S, D’Amario D, D’Alessandro DA, Michler RE, Dimmeler S, Zeiher AM, Urbanek K, Hintze TH, Kajstura J, Anversa P (2009) Identification of a coronary vascular progenitor cell in the human heart. Proc Natl Acad Sci U S A 106(37):15885–15890
Beigi F, Schmeckpeper J, Pow-Anpongkul P, Payne JA, Zhang L, Zhang Z, Huang J, Mirotsou M, Dzau VJ (2013) C3orf58, a novel paracrine protein, stimulates cardiomyocyte cell-cycle progression through the PI3K-AKT-CDK7 pathway. Circ Res 113(4):372–380
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 (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114(6):763–776
Beqqali A, Kloots J, Ward-van Oostwaard D, Mummery C, Passier R (2006) Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells 24(8):1956–1967
Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102
Bergmann O, Zdunek S, Frisén J, Bernard S, Druid H, Jovinge S (2012) Cardiomyocyte renewal in humans. Circ Res 110:e17–e18
Bicknell KA, Coxon CH, Brooks G (2004) Forced expression of the cyclin B1–CDC2 complex induces proliferation in adult rat cardiomyocytes. Biochem J 382:411–416
Bishop AE, Buttery LD, Polak JM (2002) Embryonic stem cells. J Pathol 197(4):424–429
Bolli R, Chugh AR, D’Amario D, Loughran JH, Stoddard MF, Ikram S, Beache GM, Wagner SG, Leri A, Hosoda T, Sanada F, Elmore JB, Goichberg P, Cappetta D, Solankhi NK, Fahsah I, Rokosh DG, Slaughter MS, Kajstura J, Anversa P (2011) Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 378(9806):1847–1857
Boon RA, Dimmeler S (2015) MicroRNAs in myocardial infarction. Nat Rev Cardiol 12(3):135–142
Boon RA, Jae N, Holdt L, Dimmeler S (2016) Long noncoding RNAs: from clinical genetics to therapeutic targets? J Am Coll Cardiol 67(10):1214–1226
Cagavi E, Bartulos O, Suh CY, Sun B, Yue Z, Jiang Z, Yue L, Qyang Y (2014) Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation. PLoS One 9(12):e110752
Cai J, Weiss ML, Rao MS (2004) In search of “stemness”. Exp Hematol 32(7):585–598
Campa VM, Gutierrez-Lanza R, Cerignoli F, Diaz-Trelles R, Nelson B, Tsuji T, Barcova M, Jiang W, Mercola M (2008) Notch activates cell cycle reentry and progression in quiescent cardiomyocytes. J Cell Biol 183(1):129–141
Canseco DC, Kimura W, Garg S, Mukherjee S, Bhattacharya S, Abdisalaam S, Das S, Asaithamby A, Mammen PP, Sadek HA (2015) Human ventricular unloading induces cardiomyocyte proliferation. J Am Coll Cardiol 65:892–900
Cheng RK, Asai T, Tang H, Dashoush NH, Kara RJ, Costa KD, Naka Y, Wu EX, Wolgemuth DJ, Chaudhry HW (2007) Cyclin A2 induces cardiac regeneration after myocardial infarction and prevents heart failure. Circ Res 100:1741–1748
Choi SH, Jung SY, Suh W, Baek SH, Kwon SM (2013) Establishment of isolation and expansion protocols for human cardiac C-kit-positive progenitor cells for stem cell therapy. Transplant Proc 45(1):420–426
Chong JJ, Chandrakanthan V, Xaymardan M, Asli NS, Li J, Ahmed I, Heffernan C, Menon MK, Scarlett CJ, Rashidianfar A, Biben C, Zoellner H, Colvin EK, Pimanda JE, Biankin AV, Zhou B, Pu WT, Prall OW, Harvey RP (2011) Adult cardiac-resident MSC-like stem cells with a proepicardial origin. Cell Stem Cell 9(6):527–540
Di Meglio F, Castaldo C, Nurzynska D, Miraglia R, Romano V, Russolillo V, Giuseppina L, Vosa C, Montagnani S (2010a) Localization and origin of cardiac CD117-positive cells: identification of a population of epicardially-derived cells in adult human heart. Ital J Anat Embryol 115(1–2):71–78
Di Meglio F, Castaldo C, Nurzynska D, Romano V, Miraglia R, Bancone C, Langella G, Vosa C, Montagnani S (2010b) Epithelial-mesenchymal transition of epicardial mesothelium is a source of cardiac CD117-positive stem cells in adult human heart. J Mol Cell Cardiol 49(5):719–727
Dixit P, Katare R (2015) Challenges in identifying the best source of stem cells for cardiac regeneration therapy. Stem Cell Res Ther 6(1):26
D’Uva G, Aharonov A, Lauriola M, Kain D, Yahalom-Ronen Y, Carvalho S, Weisinger K, Bassat E, Rajchman D, Yifa O, Lysenko M, Konfino T, Hegesh J, Brenner O, Neeman M, Yarden Y, Leor J, Sarig R, Harvey RP, Tzahor E (2015) ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nat Cell Biol 17(5):627–638
Ema M, Takahashi S, Rossant J (2006) Deletion of the selection cassette, but not cis-acting elements, in targeted Flk1-lacZ allele reveals Flk1 expression in multipotent mesodermal progenitors. Blood 107(1):111–117
Engleka KA, Manderfield LJ, Brust RD, Li L, Cohen A, Dymecki SM, Epstein JA (2012) Islet1 derivatives in the heart are of both neural crest and second heart field origin. Circ Res 110(7):922–926
Fatkhudinov T, Bol’shakova GB, Goldshtein DV, Sukhikh GT (2014) Mechanisms of therapeutic activity of multipotent cells in heart diseases. Bull Exp Biol Med 156(4):535–543
Gai H, Leung EL, Costantino PD, Aguila JR, Nguyen DM, Fink LM, Ward DC, Ma Y (2009) Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts. Cell Biol Int 33(11):1184–1193
Garbern JC, Lee RT (2013) Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell 12(6):689–698
Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183(4):1797–1806
Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401(6751):390–394
Hatt CR, Jain AK, Parthasarathy V, Lang A, Raval AN (2013) MRI-3D ultrasound-X-ray image fusion with electromagnetic tracking for transendocardial therapeutic injections: in-vitro validation and in-vivo feasibility. Comput Med Imaging Graph 37(2):162–173
Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, Martin JF (2011) Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science 332:458–461
Hierlihy AM, Seale P, Lobe CG, Rudnicki MA, Megeney LA (2002) The post-natal heart contains a myocardial stem cell population. FEBS Lett 530(1–3):239–243
Hong KU, Guo Y, Li QH, Cao P, Al-Maqtari T, Vajravelu BN, Du J, Book MJ, Zhu X, Nong Y, Bhatnagar A, Bolli R (2014) c-kit+ Cardiac stem cells alleviate post-myocardial infarction left ventricular dysfunction despite poor engraftment and negligible retention in the recipient heart. PLoS One 9(5):e96725
Hosoda T, D’Amario D, Cabral-Da-Silva MC, Zheng H, Padin-Iruegas ME, Ogorek B, Ferreira-Martins J, Yasuzawa-Amano S, Amano K, Ide-Iwata N, Cheng W, Rota M, Urbanek K, Kajstura J, Anversa P, Leri A (2009) Clonality of mouse and human cardiomyogenesis in vivo. Proc Natl Acad Sci U S A 106(40):17169–17174
Iida M, Heike T, Yoshimoto M, Baba S, Doi H, Nakahata T (2005) Identification of cardiac stem cells with FLK1, CD31, and VE-cadherin expression during embryonic stem cell differentiation. FASEB J 19(3):371–378
Ishitobi H, Wakamatsu A, Liu F, Azami T, Hamada M, Matsumoto K, Kataoka H, Kobayashi M, Choi K, Nishikawa S, Takahashi S, Ema M (2011) Molecular basis for Flk1 expression in hemato-cardiovascular progenitors in the mouse. Development 138(24):5357–5368
Jackson T, Allard MF, Sreenan CM (1990) The c-myc proto-oncogene regulates cardiac development in transgenic mice. Mol Cell Biol 10(7):3709–3716
Jessup M, Brozena S (2003) Heart failure. N Engl J Med 348(20):2007–2018
Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, Konstam MA, Mancini DM, Rahko PS, Silver MA, Stevenson LW, Yancy CW (2009) 2009 focused update: ACCF/AHA guidelines for the diagnosis and Management of Heart Failure in adults: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circ Res 119(14):1977–1916
Jha AK, Tharp KM, Ye J, Santiago-Ortiz JL, Jackson WM, Stahl A, Schaffer DV, Yeghiazarians Y, Healy KE (2015) Enhanced survival and engraftment of transplanted stem cells using growth factor sequestering hydrogels. Biomaterials 47:1–12
Jung J, Kim TG, Lyons GE, Kim HR, Lee Y (2005) Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma protein. J Biol Chem 280(35):30916–30923
Kajstura J, Urbanek K, Perl S, Hosoda T, Zheng H, Ogórek B, Ferreira-Martins J, Goichberg P, Rondon-Clavo C, Sanada F, D’Amario D, Rota M, Del Monte F, Orlic D, Tisdale J, Leri A, Anversa P (2010) Cardiomyogenesis in the adult human heart. Circ Res 107:305–315
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(5):723–732
Kazakov A, Meier T, Werner C, Hall R, Klemmer B, Korbel C, Lammert F, Maack C, Bohm M, Laufs U (2015) C-kit(+) resident cardiac stem cells improve left ventricular fibrosis in pressure overload. Stem Cell Res 15(3):700–711
Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108(3):407–414
Keith MC, Tang XL, Tokita Y, Li QH, Ghafghazi S, Moore Iv J, Hong KU, Elmore B, Amraotkar A, Ganzel BL, Grubb KJ, Flaherty MP, Hunt G, Vajravelu B, Wysoczynski M, Bolli R (2015) Safety of intracoronary infusion of 20 million C-kit positive human cardiac stem cells in pigs. PLoS One 10(4):e0124227
Kelly RG, Buckingham ME (2002) The anterior heart-forming field: voyage to the arterial pole of the heart. Trends Genet 18(4):210–216
Kensah G, Roa Lara A, Dahlmann J, Zweigerdt R, Schwanke K, Hegermann J, Skvorc D, Gawol A, Azizian A, Wagner S, Maier LS, Krause A, Drager G, Ochs M, Haverich A, Gruh I, Martin U (2013) Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro. Eur Heart J 34(15):1134–1146
Kocabas F, Mahmoud AI, Sosic D, Porrello ER, Chen R, Garcia JA, DeBerardinis RJ, Sadek HA (2012) The hypoxic epicardial and subepicardial microenvironment. J Cardiovasc Transl Res 5(5):654–665
Kocabas F, Mahmoud AI, Muralidhar SA, Kimura W, Koura AS, Thet S, Porrello ER, Sadek HA (2013) Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Nature 497(7448):249–253
Kubin T, Pöling J, Kostin S, Gajawada P, Hein S, Rees W, Wietelmann A, Tanaka M, Lörchner H, Schimanski S, Szibor M, Warnecke H, Braun T (2011) Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling. Cell Stem Cell 9:420
Kühn B, Monte F d, Hajjar RJ, Chang Y-S, Lebeche D, Arab S, Keating MT (2007) Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat Med 13:962–969
Larrivee B, Olive PL, Karsan A (2006) Tissue distribution of endothelial cells in vivo following intravenous injection. Exp Hematol 34(12):1741–1745
Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433(7026):647–653
Lee JH, Lee JB, Shapovalova Z, Fiebig-Comyn A, Mitchell RR, Laronde S, Szabo E, Benoit YD, Bhatia M (2014) Somatic transcriptome priming gates lineage-specific differentiation potential of human-induced pluripotent stem cell states. Nat Commun 5:5605
Leobon B, Garcin I, Menasche P, Vilquin JT, Audinat E, Charpak S (2003) Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc Natl Acad Sci U S A 100(13):7808–7811
Leri A, Kajstura J, Anversa P (2011) Role of cardiac stem cells in cardiac pathophysiology: a paradigm shift in human myocardial biology. Circ Res 109(8):941–961
Leri A, Rota M, Hosoda T, Goichberg P, Anversa P (2014) Cardiac stem cell niches. Stem Cell Res 13(3 Pt B):631–646
Li RK, Jia ZQ, Weisel RD, Mickle DA, Zhang J, Mohabeer MK, Rao V, Ivanov J (1996) Cardiomyocyte transplantation improves heart function. Ann Thorac Surg 62(3):654–660. discussion 660-651
Liang SX, Tan TY, Gaudry L, Chong B (2010) Differentiation and migration of Sca1+/CD31- cardiac side population cells in a murine myocardial ischemic model. Int J Cardiol 138(1):40–49
Limana F, Zacheo A, Mocini D, Mangoni A, Borsellino G, Diamantini A, De Mori R, Battistini L, Vigna E, Santini M, Loiaconi V, Pompilio G, Germani A, Capogrossi MC (2007) Identification of myocardial and vascular precursor cells in human and mouse epicardium. Circ Res 101(12):1255–1265
Linke A, Muller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, Castaldo C, Cascapera S, Bohm M, Quaini F, Urbanek K, Leri A, Hintze TH, Kajstura J, Anversa P (2005) Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A 102(25):8966–8971
Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA, Bassel-Duby R, Olson EN (2008) microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev 22(23):3242–3254
Maher TJ, Ren Y, Li Q, Braunlin E, Garry MG, Sorrentino BP, Martin CM (2014) ATP-binding cassette transporter Abcg2 lineage contributes to the cardiac vasculature after oxidative stress. Am J Physiol Heart Circ Physiol 306(12):H1610–H1618
Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, Czer LS, Marban L, Mendizabal A, Johnston PV, Russell SD, Schuleri KH, Lardo AC, Gerstenblith G, Marban E (2012) Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379(9819):895–904
Marelli D, Desrosiers C, el-Alfy M, Kao RL, Chiu RC (1992) Cell transplantation for myocardial repair: an experimental approach. Cell Transplant 1(6):383–390
Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, Nakaya H, Kasanuki H, Komuro I (2004) Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279(12):11384–11391
Menasche P (2004) Embryonic stem cells pace the heart. Nat Biotechnol 22(10):1237–1238
Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, Vilquin JT, Marolleau JP, Seymour B, Larghero J, Lake S, Chatellier G, Solomon S, Desnos M, Hagege AA (2008) The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117(9):1189–1200
Menasche P, Vanneaux V, Hagege A, Bel A, Cholley B, Cacciapuoti I, Parouchev A, Benhamouda N, Tachdjian G, Tosca L, Trouvin JH, Fabreguettes JR, Bellamy V, Guillemain R, Suberbielle Boissel C, Tartour E, Desnos M, Larghero J (2015) Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. Eur Heart J 36(30):2011–2017
Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL (1997) Identification of a lineage of multipotent hematopoietic progenitors. Development 124(10):1929–1939
Motoike T, Markham DW, Rossant J, Sato TN (2003) Evidence for novel fate of Flk1+ progenitor: contribution to muscle lineage. Genesis 35(3):153–159
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB, American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2015) Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation 131(4):e29–322
Murry CE, Wiseman RW, Schwartz SM, Hauschka SD (1996) Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest 98:2512–2523
Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428(6983):664–668
Mushtaq M, DiFede DL, Golpanian S, Khan A, Gomes SA, Mendizabal A, Heldman AW, Hare JM (2014) Rationale and design of the percutaneous stem cell injection delivery effects on Neomyogenesis in dilated cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy. J Cardiovasc Transl Res 7(9):769–780
Novoyatleva T, Diehl F, Amerongen MJ v, Patra C, Ferrazzi F, Bellazzi R, Engel FB (2010) TWEAK is a positive regulator of cardiomyocyte proliferation. Cardiovasc Res 85:681
Oberpriller JO, Oberpriller JC (1974) Response of the adult newt ventricle to injury. J Exp Zool A Ecol Genet Physiol 187(2):249–259
Oettgen P, Boyle AJ, Schulman SP, Hare JM (2006) Cardiac stem cell therapy. Need for optimization of efficacy and safety monitoring. Circulation 114(4):353–358
Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 100(21):12313–12318
O’Meara CC, Wamstad JA, Gladstone RA, Fomovsky GM, Butty VL, Shrikumar A, Gannon JB, Boyer LA, Lee RT (2015) Transcriptional reversion of cardiac myocyte fate during mammalian cardiac regeneration. Circ Res 116(5):804–815
Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P (2001a) Transplanted adult bone marrow cells repair myocardial infarcts in mice. Ann N Y Acad Sci 938:221–230
Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001b) Bone marrow cells regenerate infarcted myocardium. Nature 410(6829):701–705
Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P (2003) Bone marrow stem cells regenerate infarcted myocardium. Pediatr Transplant 7(Suppl 3):86–88
Ott HC, Matthiesen TS, Brechtken J, Grindle S, Goh SK, Nelson W, Taylor DA (2007) The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells. Nat Clin Pract Cardiovasc Med 4(Suppl 1):S27–S39
Pasumarthi KBS, Nakajima H, Nakajima HO, Soonpaa MH, Field LJ (2005) Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice. Circ Res 96:110–118
Perin EC, Silva GV, Henry TD, Cabreira-Hansen MG, Moore WH, Coulter SA, Herlihy JP, Fernandes MR, Cheong BY, Flamm SD, Traverse JH, Zheng Y, Smith D, Shaw S, Westbrook L, Olson R, Patel D, Gahremanpour A, Canales J, Vaughn WK, Willerson JT (2011) A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF). Am Heart J 161(6):1078–1087. e1073
Pfister O, Mouquet F, Jain M, Summer R, Helmes M, Fine A, Colucci WS, Liao R (2005) CD31- but not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ Res 97(1):52–61
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147
Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA (2011) Transient regenerative potential of the neonatal mouse heart. Science 331:1078–1080
Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298:2188–2190
Reinecke H, Bogdanski J, Woltering A, Breithardt G, Assmann G, Kerber S, Eckardstein A v (2002a) Relation of serum levels of sex hormone binding globulin to coronary heart disease in postmenopausal women. Am J Cardiol 90(4):364–368
Reinecke H, Poppa V, Murry CE (2002b) Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting. J Mol Cell Cardiol 34(2):241–249
Rochais F, Sturny R, Chao CM (2014) FGF10 promotes regional foetal cardiomyocyte proliferation and adult cardiomyocyte cell-cycle re-entry. Cardiovasc Res 104:432–442
Rumyantsev PP (1966) Autoradiographic study on the synthesis of DNA, RNA, and proteins in normal cardiac muscle cells and those changed by experimental injury. Folia Histochem Cytochem 4:397–424
Rumyantsev PP (1973) Post-injury DNA synthesis, mitosis and ultrastructural reorganization of adult frog cardiac myocytes. An electron microscopic-autoradiographic study. Z Zellforsch Mik Ana 139:431–450
Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK (2013) Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493(7432):433–436
Smart N, Bollini S, Dube KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR (2011) De novo cardiomyocytes from within the activated adult heart after injury. Nature 474(7353):640–644
Sullivan KE, Burns LJ, Black LD 3rd (2015) An in vitro model for the assessment of stem cell fate following implantation within the infarct microenvironment identifies ISL-1 expression as the strongest predictor of c-kit(+) cardiac progenitor cells’ therapeutic potential. J Mol Cell Cardiol 88:91–100
Suresh R, Chiriac A, Goel K, Villarraga HR, Lopez-Jimenez F, Thomas RJ, Terzic A, Nelson TJ, Perez-Terzic C (2013) CXCR4+ and FLK-1+ identify circulating cells associated with improved cardiac function in patients following myocardial infarction. J Cardiovasc Transl Res 6(5):787–797
Suzuki K, Murtuza B, Suzuki N, Smolenski RT, Yacoub MH (2001) Intracoronary infusion of skeletal myoblasts improves cardiac function in doxorubicin-induced heart failure. Circulation 104(12 Suppl 1):I213–I217
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676
Tateishi K, Ashihara E, Takehara N, Nomura T, Honsho S, Nakagami T, Morikawa S, Takahashi T, Ueyama T, Matsubara H, Oh H (2007) Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration. J Cell Sci 120(Pt 10):1791–1800
Tillmanns J, Rota M, Hosoda T, Misao Y, Esposito G, Gonzalez A, Vitale S, Parolin C, Yasuzawa-Amano S, Muraski J, De Angelis A, Lecapitaine N, Siggins RW, Loredo M, Bearzi C, Bolli R, Urbanek K, Leri A, Kajstura J, Anversa P (2008) Formation of large coronary arteries by cardiac progenitor cells. Proc Natl Acad Sci U S A 105(5):1668–1673
Tseliou E, de Couto G, Terrovitis J, Sun B, Weixin L, Marban L, Marban E (2014) Angiogenesis, cardiomyocyte proliferation and anti-fibrotic effects underlie structural preservation post-infarction by intramyocardially-injected cardiospheres. PLoS One 9(2):e88590
Turan RD, Aslan GS, Yucel D, Doger R, Kocabas F (2016) Evolving approaches to heart regeneration by therapeutic stimulation of resident cardiomyocyte cell cycle. Anatol J Cardiol 16(11):881–886
Uchida S, De Gaspari P, Kostin S, Jenniches K, Kilic A, Izumiya Y, Shiojima I, Grosse Kreymborg K, Renz H, Walsh K, Braun T (2013) Sca1-derived cells are a source of myocardial renewal in the murine adult heart. Stem Cell Reports 1(5):397–410
Unno K, Jain M, Liao R (2012) Cardiac side population cells: moving toward the center stage in cardiac regeneration. Circ Res 110(10):1355–1363
Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A, Hosoda T, Chimenti S, Baker M, Limana F, Nurzynska D, Torella D, Rotatori F, Rastaldo R, Musso E, Quaini F, Leri A, Kajstura J, Anversa P (2005) Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 97(7):663–673
Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, Cernelc P, Torre-Amione G, Haddad F, Wu JC (2013) Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation 128(11 Suppl 1):S42–S49
Weinberger F, Mehrkens D, Friedrich FW, Stubbendorff M, Hua X, Muller JC, Schrepfer S, Evans SM, Carrier L, Eschenhagen T (2012) Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart. Circ Res 110(10):1303–1310
Witman N, Murtuza B, Davis B, Arner A, Morrison JI (2011) Recapitulation of developmental cardiogenesis governs the morphological and functional regeneration of adult newt hearts following injury. Dev Biol 354:67–76
Wu SM, Chien KR, Mummery C (2008) Origins and fates of cardiovascular progenitor cells. Cell 132(4):537–543
Yacoub MH, Terrovitis J (2013) CADUCEUS, SCIPIO, ALCADIA: cell therapy trials using cardiac-derived cells for patients with post myocardial infarction LV dysfunction, still evolving. Glob Cardiol Sci Pract 2013(1):5–8
Yamashita JK, Takano M, Hiraoka-Kanie M, Shimazu C, Peishi Y, Yanagi K, Nakano A, Inoue E, Kita F, Nishikawa S (2005) Prospective identification of cardiac progenitors by a novel single cell-based cardiomyocyte induction. FASEB J 19(11):1534–1536
Yu SP, Wei Z, Wei L (2013) Preconditioning strategy in stem cell transplantation therapy. Transl Stroke Res 4(1):76–88
Zhang J, Wilson GF, Soerens AG, Koonce CH, Yu J, Palecek SP, Thomson JA, Kamp TJ (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 104(4):e30–e41
Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, Gise A v, Ikeda S, Chien KR, Pu WT (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454(7200):109–113
Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, Siuzdak G, Scholer HR, Duan L, Ding S (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4(5):381–384
Zimmet H, Porapakkham P, Porapakkham P, Sata Y, Haas SJ, Itescu S, Forbes A, Krum H (2012) Short- and long-term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST-segment elevation myocardial infarction: a meta-analysis of randomized control trials. Eur J Heart Fail 14(1):91–105
Zwi L, Caspi O, Arbel G, Huber I, Gepstein A, Park IH, Gepstein L (2009) Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation 120(15):1513–1523
Acknowledgments
We apologize to colleagues whose work could not be cited and discussed because of space limitations.
Compliance with Ethical Standards: Funding
We thank the support from Co-Funded Brain Circulation Scheme by The Scientific and Technological Research Council of Turkey (TÜBİTAK) and The Marie Curie Action COFUND of the 7th. Framework Programme (FP7) of the European Commission [grant number 115C039], TÜBİTAK ARDEB 1001 [grant numbers 115S185 & 215Z069], TÜBİTAK ARDEB 3501 [grant number 215Z071], TÜBİTAK ARDEB 1002 [grant number 216S317], The Science Academy Young Scientist Award Program (BAGEP-2015, Turkey), The International Centre for Genetic Engineering and Biotechnology – ICGEB 2015 Early Career Return Grant [grant number CRP/TUR15-02_EC], Medicines for Malaria Venture - Pathogenbox Award (supported by Bill & Melinda Gates Foundation) and funds provided by Yeditepe University, Istanbul, Turkey.
Conflict of Interest Statement
All authors declare that they have no conflicts of interest concerning this work.
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This article does not contain any studies with human participants or animals performed by any of the authors.
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This article does not contain any studies with human participants or animals performed by any of the authors.
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Arbatlı, S., Aslan, G.S., Kocabaş, F. (2017). Stem Cells in Regenerative Cardiology. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 1. Advances in Experimental Medicine and Biology(), vol 1079. Springer, Cham. https://doi.org/10.1007/5584_2017_113
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