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ISSN 0188-2198 (Impreso)

2012, Número 2

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Rev Mex Cardiol 2012; 23 (2)


Terapia celular y regeneración cardiaca. ¿Dónde estamos?

Lara-Martínez LA, Navarro-Betancourt JR, Hernández-Gutiérrez S

Idioma: Español
Referencias bibliográficas: 63
Paginas: 72-79
Archivo PDF: 67.98 Kb.


RESUMEN

La terapia celular es un recurso prometedor para el tratamiento de la cardiopatía isquémica; mediante un procedimiento como la infusión directa o intravascular de células troncales al tejido dañado, es posible restituir la capacidad funcional del corazón. A pesar del éxito de los ensayos en animales, en humanos no se han obtenido los resultados esperados; además, se presenta una serie de limitantes éticas y prácticas que ponen en duda los resultados. Se ha comprobado que la terapia con células troncales mejora las propiedades electromecánicas del tejido cardiaco como tal; sin embargo, el beneficio funcional aún es poco convincente, pero no desalentador. La realización de ensayos clínicos más grandes y el perfeccionamiento de técnicas de seguimiento no invasivas son necesarios para evaluar de manera integral el beneficio de la terapia celular. Por otra parte, el problema de la supervivencia de las células injertadas es un conflicto relevante, lo que hace que la eficiencia de las células a transferir sea variable y generalmente baja; esto es causado principalmente por tres procesos: apoptosis, isquemia e inflamación. Hasta ahora, el mecanismo más prometedor para incrementar la viabilidad del injerto es la sobreexpresión de proteínas antiapoptóticas. Sin duda, el principal desafío para la terapia celular será determinar la estirpe más adecuada para el tratamiento. En esta revisión se describen los principales tipos de células que a la fecha han sido propuestas para la regeneración cardiaca: las células troncales embrionarias, las células pluripotentes inducidas, las células derivadas de médula ósea, los mioblastos esqueléticos y las células de tejido adiposo, entre otras.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. World Health Organization. Media centre; fact sheets. Junio 2011. Disponible en: http://www.who.int/mediacentre/factsheets/fs310/en/

  2. Reffelmann T, Dow JS, Dai W, Hale SL, Simkhovich BZ, Kloner RA. Transplantation of neonatal cardiomyocytes after permanent coronary artery occlusion increases regional blood flow of infarcted myocardium. J Mol Cell Cardiol 2003; 35: 607–613.

  3. Laflamme MA, Murry CE. Regenerating the heart. Nat Biotechnol 2005; 23: 845–856.

  4. Albarrán A. Angioplastia de rescate, cateterismo sistemático tras fibrinólisis y angioplastia primaria después de 12 horas. Impacto en la estancia hospitalaria y en el pronóstico. Rev Esp Cardiol 2009; 09(Supl. C): 54-61.

  5. Aguilar J et al. Infarto agudo de miocardio. Rev Pac Med Fam 2008; 5: 102-114.

  6. Katrina A Bicknell KA, Brooks G. Reprogramming the cell cycle machinery to treat cardiovascular disease. Curr Op Pharmacol 2008; 8: 193–201.

  7. Tang J, Wang J, Kong X, Yang J et al. Vascular endothelial growth factor promotes cardiac stem cell migration via the PI3K/Akt pathway. Exp Cell Res 2009; 315: 3521-3531.

  8. Oh H, Bradfute SB, Gallardo TD, Nakamura T, GaussinV, Mishina Y et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Nat Acad Sci USA 2003; 100: 12313-12318.

  9. Beltrami AP, Barlucchi L, Torella D, Baker M et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763–776.

  10. Klug MG, Soonpaa MH, Koh GY, Field LJ. Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J Clin Invest 1996; 98: 216-224.

  11. Laflamme MA, Gold J, Xu C, Hassanipour M, Rosler E et al. Formation of human myocardium in the rat heart from human embryonic stem cells. Am J Pathol 2005; 167: 663-671.

  12. Tambara K, Sakakibara Y, Sakaguchi G, Lu F et al. Transplanted skeletal myoblasts can fully replace the infarcted. Circulation 2003; 108(Suppl 1); II259-II263.

  13. Murry CE, Field LJ, Menasche P. Cell-based cardiac repair: reflections at the 10-year point. Circulation 2005; 112: 3174-3183.

  14. Laflamme MA, Zibinden S, Epstein SE, Murry CE. Cell-based therapy for myocardial ischemia and infarction: pathophysiological mechanisms. J Mol Cel Cardiol 2008; 45: 567–581.

  15. Marelli D, Desrosiers C, el-Alfy M, Kao RL, Chiu RC. Cell transplantation for myocardial repair: an experimental approach. Cell Transplant 1992; 1: 383-390.

  16. Chiu RC, Zibaitis A, Kao RL. Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg 1995; 60: 12-18.

  17. Koh GY, Klug MG, Soonpaa MH, Field LJ. Differentiation and long-term survival of C2C12 myoblast grafts in heart. J Clin Invest 1993; 92: 1548–1554.

  18. Scorsin M, Hagege A, Vilquin JT, Fiszman M et al. Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. J Thorac Cardiovasc Surg 2000; 119: 1169-1175.

  19. Leor J, Patterson M, Quinones MJ, Kedes LH, Kloner RA. Transplantation of fetal myocardial tissue into the infarcted myocardium of rat. A potential method for repair of infarcted myocardium? Circulation 1996; 94(Suppl): 332-336.

  20. Li RK, Jia ZQ, Weisel RD, Mickle DA et al. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg 1996; 62: 654-660.

  21. Hutcheson KA, Atkins BZ, Hueman MT, Hopkins MB, Glower DD, Taylor DA. Comparison of benefits on myocardial performance of cellular cardiomyoplasty with skeletal myoblasts and fibroblasts. Cell Transplant 2000; 9: 359-368.

  22. Yasuda T, Weisel RD, Kiani C, Mickle DA, Maganti M, Li RK. Quantitative analysis of survival of transplanted smooth muscle cells with real-time polymerase chain reaction. J Thorac Cardiovasc Surg 2005; 129: 904-911.

  23. Penn MS, Francis GS, Ellis SG, Young JB, McCarthy PM, Topol EJ. Autologous cell transplantation for the treatment of damaged myocardium. Prog Cardiovasc Dis 2002; 45: 21-32.

  24. Nygren JM, Jovinge S, Breitbach M, Sawen P et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 2004; 10: 494-501.

  25. 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: 93-98.

  26. Kocher AA, Schuster MD, Szabolcs MJ, Takuma S et al. Neovascularization of ischemic myocardium by human bone marrowderived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7: 430-436.

  27. Laflamme MA, Chen KY, Naumova AV, Muskheli V et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 2007; 25: 1015-1024.

  28. Xu C, Police S, Rao N, Carpenter MK. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res 2002; 91: 501–508.

  29. Kehat I, Kenyagin-Karsenti D, Snir M, Segev H et al. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 2001; 108: 407-414.

  30. Oh Y, Wei H, Ma D, Sun X, Liew R. Clinical applications of patient-specific induced pluripotent stem cells in cardiovascular medicine. Heart 2012; 98: 443-449.

  31. Reinecke H, MacDonald GH, Hauschka SD, Murry CE. Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. J Cell Biol 2000; 149: 731-740.

  32. Etzion S, Battler A, Barbash IM, Cagnano E et al. Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. J Mol Cell Cardiol 2001; 33: 1321-1330.

  33. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.

  34. Muller-Ehmsen J, Whittaker P, Kloner RA, Dow JS et al. Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. J Mol Cell Cardiol 2002; 34: 107–116.

  35. Hudson W, Collins MC, de Freitas D, Sun YS, Muller-Borer B, Kypson AP. Beating and arrested intramyocardial injections are associated with significant mechanical loss: implications for cardiac cell transplantation. J Surg Res 2007; 142: 263-267.

  36. Robey TE, Saiget MK, Reinecke H, Murry CE. Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol 2008; 45: 567-581.

  37. Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE. Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol 2001; 33: 907–921.

  38. Suzuki K, Murtuza B, Beauchamp JR, Brand NJ et al. Role of interleukin-1beta in acute inflammation and graft death after cell transplantation to the heart. Circulation 2004; 110(Suppl 1): 219-224.

  39. Hayashi M, Li TS, Ito H, Mikamo A, Hamano K. Comparison of intramyocardial and intravenous routes of delivering bone marrow cells for the treatment of ischemic heart disease: an experimental study. Cell Transplant 2004; 13: 639-647.

  40. Freyman T, Polin G, Osman H, Crary J et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 2006; 27: 1114–1122.

  41. Yuan J, Lipinski M, Degterev A. Diversity in the mechanisms of neuronal cell death. Neuron 2003; 40: 401-413.

  42. Xu Y et al. Efficient commitment to functional CD34+ progenitor cells from human bone marrow mesenchymal stem-cell-derived induced pluripotent stem cells. PLoS One 2012;7:e34321.

  43. Zvibel I, Smets F, Soriano H. Anoikis: roadblock to cell transplantation? Cell Transplant 2002; 11: 621-630.

  44. Reddig PJ, Juliano RL. Clinging to life: cell to matrix adhesion and cell survival. Cancer Metast Rev 2005; 24: 425-439.

  45. Wong SS, Bernstein HS. Cardiac regeneration using human embryonic stem cells: producing cells for future therapy. Regen Med 2010; 5: 763-775.

  46. Pouzet B, Vilquin JT, Hagege AA, Scorsin M et al. Factors affecting functional outcome after autologous skeletal myoblast transplantation. Ann Thorac Surg 2001; 71: 844-850.

  47. Cousin B, André M, Arnaud E, Pénicaud L, Casteilla L. Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochem Biophys Res Commun 2003; 301: 1016-1022.

  48. Mani K. Programmed cell death in cardiac myocytes: strategies to maximize post-ischemic salvage. Heart Fail Rev 2009; 13: 193-209.

  49. Potts MB, Vaughn AE, McDonough H, Patterson C, Deshmukh M. Reduced Apaf-1 levels in cardiomyocytes engage strict regulation of apoptosis by endogenous XIAP. J Cell Biol 2005; 71: 925–930.

  50. Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 2007; 204: 3037–3047.

  51. Freyman T, Polin G, Osman H, Crary J et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 2006; 27: 1114-1122.

  52. Hofmann M, Wollert KC, Meyer GP, Menke A et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 2005; 111: 2198-2202.

  53. Hou D, Youssef EA, Brinton TJ, Zhang P et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005; 112: 150-156.

  54. Penn MS, Mangi AA. Genetic enhancement of stem cell engraftment, survival, and efficacy. Circ Res 2008; 102: 1471-1482.

  55. Song H, Kwon K, Lim S, Kang SM et al. Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. Mol Cell 2005; 19: 402-407.

  56. Wang X, Zhao T, Huang W, Wang T et al. Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors. Stem Cells 2009; 27: 3021-3031.

  57. Deng J, Han Y, Yan C, Tian X et al. Overexpressing cellular repressor of E1A-stimulated genes protects mesenchymal stem cells against hypoxia- and serum deprivation-induced apoptosis by activation of PI3K/Akt. Apoptosis 2010; 15: 463-473.

  58. Zeng B, Ren X, Lin G, Zhu C et al. Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement. Cell Biol Int 2008; 32: 1256-1264.

  59. Fan L, Lin C, Zhuo S, Chen L et al. Transplantation with surviving engineered mesenchymal stem cells results in better prognosis in a rat model of myocardial infarction. Eur J Heart Fail 2009; 11: 1023-1030.

  60. Li W, Ma N, Ong LL, Nesselman C et al. Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells 2007; 25: 2118-2127.

  61. Chin SP, Poey AC, Wong CY, Chang SK et al. Intramyocardial and intracoronary autologous bone marrow-derived mesenchymal stromal cell treatment in chronic severe dilated cardiomyopathy. Cytotherapy 2011; 13: 814-821.

  62. Quevedo HC, Hatzistergos KE, Oskouei BN, Feigenbaum GS. Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Nat Acad Sci USA 2009; 106: 14022-14027.

  63. Hosoda T. C-kit-positive cardiac stem cells and myocardial regeneration. Am J Cardiovasc Dis 2012; 2: 58–67.




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