Myoblast transplantation for heart failure – From bench to bedside
Heart failure causes morbidity and mortality. Cell transplantation using skeletal muscle myoblast is promising for myocardial repair as it can regenerate and repair the injury. Skeletal myoblasts are unipotent progenitor cells that can be expanded and genetically modified to deliver angiogenic cytok...
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Published in | Cirugía cardiovascular Vol. 12; no. 3; pp. 209 - 214 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English Spanish |
Published |
Elsevier España
01.07.2005
Elsevier |
Subjects | |
Online Access | Get full text |
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Abstract | Heart failure causes morbidity and mortality. Cell transplantation using skeletal muscle myoblast is promising for myocardial repair as it can regenerate and repair the injury. Skeletal myoblasts are unipotent progenitor cells that can be expanded and genetically modified to deliver angiogenic cytokines and growth factors to encourage angiomyogenesis. Myoblast transplantation inhibits ventricular remodelling, decreases left ventricular diastolic dimension, increases myocardial wall thickness and minimizes global ventricular dilatation in animals. Ongoing trials with skeletal myoblast transplantation show improvement in perfusion and metabolic activity. Time constraints and the problem of generating autologous skeletal myoblasts for every patient can be overcome if allogeneic skeletal myoblasts from healthy young donors can be made available. Myoblast transplantation is confronted with the problem of donor cell survival post-transplantation. Its safety and feasibility have been documented during animal and phase I studies. The only serious postoperative adverse event related to the procedure was ventricular arrhythmias. The results of phase I studies are still preliminary. Endpoint measurements highlight improvement in quality of life, reduced nitroglycerine consumption, enhanced exercise tolerance, improvement in NYHA Class and wall motion by echocardiography, and significantly reduced perfusion defects. Future directions include concerted collaborative efforts, strict inclusion and exclusion criteria, better establishment of target population. Further work needs to be done on the ideal cell type, optimal number of cells and route of administration. The most suitable time for cell transplantation after ischemic injury and optimal mode of cell delivery are evaluated. The use of cell-based techniques to assist with cardiac regeneration holds promise for the treatment of heart failure.
La insuficiencia cardíaca es causa de morbimortalidad. El trasplante celular con mioblastos de músculo esquelético es prometedor en la reparación miocárdica ya que puede regenerar la zona agredida. Los mioblastos esqueléticos son células progenitoras unipotenciales que pueden ser modificadas genéticamente para liberar citocinas angiogénicas y factores de crecimiento para favorecer la angiomiogénesis. El trasplante de mioblastos inhibe la remodelación ventricular, disminuye el diámetro telediastólico, aumenta el grosor de la pared ventricular y minimiza la dilatación ventricular en animales. Los ensayos en marcha muestran mejoría de la perfusión y actividad metabólica. El problema de la generación de mioblastos antólogos para cada paciente podría solucionarse si se dispusiese de mioblastos alogénicos de donantes jóvenes sanos. El trasplante de mioblastos tiene el problema de la supervivencia celular postrasplante. Su factibilidad y seguridad se han documentado en estudios animales y de fase I. El único evento adverso postoperatorio relacionado ha sido las arritmias ventriculares. Los resultados de estudios en fase I son preliminares. Las mediciones de puntos finales confirman una mejoría en la calidad de vida, reducción del consumo de nitroglicerina, aumento de la capacidad de ejercicio, mejoría de la clase funcional NYHA y motilidad parietal por ecocardiografía y reducción de los defectos de perfusión. Futuras direcciones incluyen esfuerzos colaborativos, criterios de inclusión y exclusión estrictos y mejor caracterización de la población diana. Se necesita trabajar más en el tipo ideal de célula, número óptimo de células y ruta de administración. Se están estudiando el momento ideal del trasplante y el modo de liberación celular. El uso de técnicas celulares para la regeneración cardíaca es prometedor en el tratamiento de la insuficiencia cardíaca. |
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AbstractList | Heart failure causes morbidity and mortality. Cell transplantation using skeletal muscle myoblast is promising for myocardial repair as it can regenerate and repair the injury. Skeletal myoblasts are unipotent progenitor cells that can be expanded and genetically modified to deliver angiogenic cytokines and growth factors to encourage angiomyogenesis. Myoblast transplantation inhibits ventricular remodelling, decreases left ventricular diastolic dimension, increases myocardial wall thickness and minimizes global ventricular dilatation in animals. Ongoing trials with skeletal myoblast transplantation show improvement in perfusion and metabolic activity. Time constraints and the problem of generating autologous skeletal myoblasts for every patient can be overcome if allogeneic skeletal myoblasts from healthy young donors can be made available. Myoblast transplantation is confronted with the problem of donor cell survival post-transplantation. Its safety and feasibility have been documented during animal and phase I studies. The only serious postoperative adverse event related to the procedure was ventricular arrhythmias. The results of phase I studies are still preliminary. Endpoint measurements highlight improvement in quality of life, reduced nitroglycerine consumption, enhanced exercise tolerance, improvement in NYHA Class and wall motion by echocardiography, and significantly reduced perfusion defects. Future directions include concerted collaborative efforts, strict inclusion and exclusion criteria, better establishment of target population. Further work needs to be done on the ideal cell type, optimal number of cells and route of administration. The most suitable time for cell transplantation after ischemic injury and optimal mode of cell delivery are evaluated. The use of cell-based techniques to assist with cardiac regeneration holds promise for the treatment of heart failure.
La insuficiencia cardíaca es causa de morbimortalidad. El trasplante celular con mioblastos de músculo esquelético es prometedor en la reparación miocárdica ya que puede regenerar la zona agredida. Los mioblastos esqueléticos son células progenitoras unipotenciales que pueden ser modificadas genéticamente para liberar citocinas angiogénicas y factores de crecimiento para favorecer la angiomiogénesis. El trasplante de mioblastos inhibe la remodelación ventricular, disminuye el diámetro telediastólico, aumenta el grosor de la pared ventricular y minimiza la dilatación ventricular en animales. Los ensayos en marcha muestran mejoría de la perfusión y actividad metabólica. El problema de la generación de mioblastos antólogos para cada paciente podría solucionarse si se dispusiese de mioblastos alogénicos de donantes jóvenes sanos. El trasplante de mioblastos tiene el problema de la supervivencia celular postrasplante. Su factibilidad y seguridad se han documentado en estudios animales y de fase I. El único evento adverso postoperatorio relacionado ha sido las arritmias ventriculares. Los resultados de estudios en fase I son preliminares. Las mediciones de puntos finales confirman una mejoría en la calidad de vida, reducción del consumo de nitroglicerina, aumento de la capacidad de ejercicio, mejoría de la clase funcional NYHA y motilidad parietal por ecocardiografía y reducción de los defectos de perfusión. Futuras direcciones incluyen esfuerzos colaborativos, criterios de inclusión y exclusión estrictos y mejor caracterización de la población diana. Se necesita trabajar más en el tipo ideal de célula, número óptimo de células y ruta de administración. Se están estudiando el momento ideal del trasplante y el modo de liberación celular. El uso de técnicas celulares para la regeneración cardíaca es prometedor en el tratamiento de la insuficiencia cardíaca. Heart failure causes morbidity and mortality. Cell transplantation using skeletal muscle myoblast is promising for myocardial repair as it can regenerate and repair the injury. Skeletal myoblasts are unipotent progenitor cells that can be expanded and genetically modified to deliver angiogenic cytokines and growth factors to encourage angiomyogenesis. Myoblast transplantation inhibits ventricular remodelling, decreases left ventricular diastolic dimension, increases myocardial wall thickness and minimizes global ventricular dilatation in animals. Ongoing trials with skeletal myoblast transplantation show improvement in perfusion and metabolic activity. Time constraints and the problem of generating autologous skeletal myoblasts for every patient can be overcome if allogeneic skeletal myoblasts from healthy young donors can be made available. Myoblast transplantation is confronted with the problem of donor cell survival post-transplantation. Its safety and feasibility have been documented during animal and phase I studies. The only serious postoperative adverse event related to the procedure was ventricular arrhythmias. The results of phase I studies are still preliminary. Endpoint measurements highlight improvement in quality of life, reduced nitroglycerine consumption, enhanced exercise tolerance, improvement in NYHA Class and wall motion by echocardiography, and significantly reduced perfusion defects. Future directions include concerted collaborative efforts, strict inclusion and exclusion criteria, better establishment of target population. Further work needs to be done on the ideal cell type, optimal number of cells and route of administration. The most suitable time for cell transplantation after ischemic injury and optimal mode of cell delivery are evaluated. The use of cell-based techniques to assist with cardiac regeneration holds promise for the treatment of heart failure. |
Author | Sim, Eugene K.W. Haider, Husnain K. Shim, Winston S.N. Tan, Genevieve M.Y. Wong, Philip Ye, Lei |
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Title | Myoblast transplantation for heart failure – From bench to bedside |
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