Cardiomiócitos (adulto, fetal e neonatal) |
Miogênese |
Integração com o tecido hospedeiro, como visto em roedores(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.) Fenótipo de cardiomiócitos adultos(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.)
|
Dilema ético Incapacidade para reproduzir(2525. Taylor DA. Cell-based myocardial repair: how should we proceed? Int J Cardiol. 2004;95 Suppl 1:S8-12. Review.) Disponibilidade limitada Imunogenicidade(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.) Curta viabilidade celular(2525. Taylor DA. Cell-based myocardial repair: how should we proceed? Int J Cardiol. 2004;95 Suppl 1:S8-12. Review.) Integração inadequada com tecido hospedeiro em suínos(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.)
|
Mioblastos esqueléticos |
Miogênese |
Autólogos Alta viabilidade celular e adesão do enxerto(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.) Fenótipo de musculatura esquelética adulta(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.) Fácil de isolar |
Alto risco de arritmias(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.) Pouca integração estrutural e fisiológica com o tecido hospedeiro(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.)
|
Células-tronco derivadas de medula óssea (mesenquimais, progenitoras endoteliais e hematopoiéticas) |
|
Multipotentes Autólogos Fáceis de isolar Alto potencial de expansão Presença de efeitos adjacentes(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.)
|
Possível angiogênese em locais indesejados(4141. Ott HC, McCue J, Taylor DA. Cell-based cardiovascular repair-the hurdles and the opportunities. Basic Res Cardiol. 2005;100(6):504-17.) Disponibilidade limitada |
Células-tronco mesenquimais |
Miogênese |
Diferenciados em fenótipo semelhante a cardiomiócitos(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.) Diferenciação em células endoteliais, conforme visto em caninos(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.) Propriedades imunossupressoras(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.) Alta integração estrutural e fisiológica com tecido hospedeiro(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.)
|
Imunogenicidade de células-tronco mesenquimais alógenas(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.)
|
Células progenitoras endoteliais |
Angiogênese |
Neovasculogênese(4848. Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease: part II: cell-based therapies. Circulation. 2004; 109(22) : 2692-7.)
|
Limitação em número e migração celular em pacientes com doenças coronárias(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.)
|
Células-tronco hematopoiéticas |
Angiogênese |
Impacto benéfico no remodelamento do ventrículo esquerdo e angiogênese(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.)
|
Incapazes de se diferenciar em cardiomiócitos(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.)
|
Células-tronco embrionárias |
Miogênese |
Alta proliferação(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.) Pluripotentes(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.) Diferenciam-se em cardiomiócitos(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.) Integram com cardiomiócitos do hospedeiro via junções comunicantes(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.) Podem ser pré-tratadas com fatores de crescimento(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.)
|
Dilema ético Risco de formação de teratoma(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.) Alta imunogenicidade(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.) Disponibilidade limitada |
Células de músculos lisos |
Miogênese |
Propriedades elásticas melhoram função cardíaca(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.)
|
Imunogenicidade(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.) Não melhoram função contrátil(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.)
|
Células-tronco derivadas de tecido adiposo |
Angiogênese Miogênese |
Multipotentes(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.) Alta disponibilidade(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.) Fáceis de isolar(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.) Alta proliferação(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.) Secretam fatores de crescimento(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.) Induzem miogênese e angiogênese(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.)
|
Adesão celular ruim a longo prazo(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.) Sem diferenciação significativa(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.)
|
Células-tronco cardíacas |
Miogênese |
Autólogas Multipotentes(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.) Expandem in vitro(38)
|
Disponibilidade limitada |
Celuals-tronco pluripotentes induzidas |
Miogênese |
Pluripotentes Autólogas Diferenciam-se em cardiomiócitos(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.) Boa disponibilidade Grande potencial de expansão |
Risco de formação de teratoma(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.)
|