Cardiomyocytes (adult, fetal and neonatal) |
Myogenesis |
Integration with the host tissue, as seen in rodents(2626. Soonpaa MH, Koh GY Klug MG, Field LJ. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science. 1994;264(5155):98-101.,2727. Li RK, Weisel RD, Mickle DA, Jia ZQ, Kim EJ, Sakai T, et al. Autologous porcine heart cell transplantation improved heart function after a myocardial infarction. J Thorac Cardiovasc Surg. 2000;119(1):62-8.) Adult cardiomyocytes' phenotype(2626. Soonpaa MH, Koh GY Klug MG, Field LJ. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science. 1994;264(5155):98-101.)
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Ethics dilemma Inability to reproduce(2525. Taylor DA. Cell-based myocardial repair: how should we proceed? Int J Cardiol. 2004;95 Suppl 1:S8-12. Review.) Limited availability Immunogenicity(1818. Wang F Guan J. Cellular cardiomyoplasty and cardiac tissue engineering for myocardial therapy. Adv Drug Deliv Rev. 2010;62(7-8):784-97. Review.) Short cell survival (2525. Taylor DA. Cell-based myocardial repair: how should we proceed? Int J Cardiol. 2004;95 Suppl 1:S8-12. Review.) Poor integration with host tissue in porcine(2727. Li RK, Weisel RD, Mickle DA, Jia ZQ, Kim EJ, Sakai T, et al. Autologous porcine heart cell transplantation improved heart function after a myocardial infarction. J Thorac Cardiovasc Surg. 2000;119(1):62-8.)
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Skeletal myoblasts |
Myogenesis |
Autologous High cell survival and engraftment(4242. Reinlib L, Field L. Cell transplantation as future therapy for cardiovascular disease?: a workshop of the National Heart, Lung, and Blood Institute. Circulation. 2000;101(18):E182-7.) Adult skeletal muscle phenotype(2828. Murry CE, Wiseman RW, Schwartz SM, Hauschka SD. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest. 1996;98(11): 2512-23.) Easy to isolate |
High risk of arrhythmias(3232. Kehat I, Khimovich L, Caspi 0, Gepstein A, Shofti R, Arbel G, et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol. 2004;22(10):1282-9.) Low structural and physiological integration with host tissue(3232. Kehat I, Khimovich L, Caspi 0, Gepstein A, Shofti R, Arbel G, et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol. 2004;22(10):1282-9.)
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Bone marrow-derived stem cells (mesenchymal stem cells, endothelial progenitor cells, hematopoietic stem cells) |
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Multipotent Autologous Easy to isolate High expansion potential Presence of paracrine effects(4343. Uemura R, Xu M, Ahmad N, Ashraf M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res. 2006;98(11):1414-21.)
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Possible angiogenesis at unwanted sites(4141. Ott HC, McCue J, Taylor DA. Cell-based cardiovascular repair-the hurdles and the opportunities. Basic Res Cardiol. 2005;100(6):504-17.) Limited availability |
Mesenchymal stem cells |
Myogenesis |
Differentiate into cardiomyocytes-like phenotype(4444. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105(1):93-8.) Differentiation into endothelial cells as seen in canines(4545. Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005;111(2):150-6.) Immunosuppressive properties(4646. Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med. 2003;9(9):1195-201.) High structural and physiological integration with host tissue(4343. Uemura R, Xu M, Ahmad N, Ashraf M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res. 2006;98(11):1414-21.,4545. Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005;111(2):150-6.)
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Immunogenicity of allogenous mesenchymal stem cells(4747. Huang XP, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel RD, et al. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation. 2010; 122(23):2419-29.)
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Endothelial progenitor cells |
Angiogenesis |
Neovasculogenesis(4848. Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease: part II: cell-based therapies. Circulation. 2004; 109(22) : 2692-7.)
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Limitations in number and migration of cells in patients with coronary artery disease(4949. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001;89(1):E1-7.)
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Hematopoietic stem cells |
Angiogenesis |
Beneficial impact on left ventricular remodeling and angiogenesis(5050. Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428(6983):664-8.)
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Incapable of differentiating into cardiomyocytes(5050. Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428(6983):664-8.)
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Embryonic stem cells |
Myogenesis |
High proliferation(5151. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145-7. Erratum in: Science. 1998;282(5395):1827.)
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Ethical dilemma |
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Pluripotent(5151. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145-7. Erratum in: Science. 1998;282(5395):1827.)
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Risk of teratoma formation(5151. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145-7. Erratum in: Science. 1998;282(5395):1827.)
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Differentiate into cardiomyocytes(3232. Kehat I, Khimovich L, Caspi 0, Gepstein A, Shofti R, Arbel G, et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol. 2004;22(10):1282-9.)
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High immunogenicity(5252. Swijnenburg RJ, Tanaka M, Vogel H, Baker J, Kofidis T, Gunawan F, et al. Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation. 2005;112(9 Suppl):I166-72.)
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Integrate with host cardiomyocytes via gap junctions(3030. Klug MG, Soonpaa MH, Koh GY Field LJ. Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts. J Clin Invest. 1996;98(1):216-24.) Can be pre-treated with pro-survival factors(3333. Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol. 2007; 25(9):1015-24.)
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Limited availability |
Smooth muscle cells |
Myogenesis |
Elastic properties improve heart function(3535. Yoo KJ, Li RK, Weisel RD, Mickle DA, Li G, Yau TM. Autologous smooth muscle cell transplantation improved heart function in dilated cardiomyopathy. Ann Thorac Surg. 2000;70(3):859-65.)
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Immunogenicity(3434. Li RK, Jia ZQ, Weisel RD, Merante F, Mickle DA. Smooth muscle cell transplantation into myocardial scar tissue improves heart function. J Mol Cell Cardiol. 1999;31(3):513-22.) Do not improve contractile function(3434. Li RK, Jia ZQ, Weisel RD, Merante F, Mickle DA. Smooth muscle cell transplantation into myocardial scar tissue improves heart function. J Mol Cell Cardiol. 1999;31(3):513-22.)
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Adipose tissue-derived stem cells |
Angiogenesis Myogenesis |
Multipotent(5353. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002; 13(12):4279-95.) High availability(3636. Planat-Benard V, Silvestre JS, Cousin B, André M, Nibbelink M, Tamarat R, et al. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation. 2004;109(5):656-63.) Easy to isolate(5353. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002; 13(12):4279-95.) High proliferation(3636. Planat-Benard V, Silvestre JS, Cousin B, André M, Nibbelink M, Tamarat R, et al. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation. 2004;109(5):656-63.) Secrete growth factors(3737. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004;109(10):1292-8.) Induce myogenesis and angiogenesis(3737. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004;109(10):1292-8.)
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Poor long-term cell engraftment(5454. Schenke-Layland K, Strem BM, Jordan MC, Deemedio MT, Hedrick MH, Roos KP, et al. Adipose tissue-derived cells improve cardiac function following myocardial infarction. J Surg Res. 2009;153(2):217-23.) No significant differentiation(5555. Rigol M, Solanes N, Farré J, Roura S, Roqué M, Berruezo A, et al. Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration. J Card Fail. 2010;16(4):357-66.)
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Cardiac stem cells |
Myogenesis |
Autologous Multipotent(3838. Barile L, Chimenti I, Gaetani R, Forte E, Miraldi F, Frati G, et al. Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration. Nat Clin Pract Cardiovasc Med. 2007;4(S1 Suppl 1):S9-14.) Expand in vitro(3838. Barile L, Chimenti I, Gaetani R, Forte E, Miraldi F, Frati G, et al. Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration. Nat Clin Pract Cardiovasc Med. 2007;4(S1 Suppl 1):S9-14.)
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Limited availability |
Induced pluripotent stem cells |
Myogenesis |
Pluripotent Autologous Differentiate into cardiomyocytes(3939. Zwi L, Caspi O, Arbel G, Huber I, Gepstein A, Park IH, et al. Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation. 2009; 120(15):1513-23.) Good availability High expansion potential |
Risk of teratoma formation(4040. Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A. Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation. 2009;120(5):408-16.)
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