RESUMO
Myocardial infarction is the major cause of death in western countries due to impaired function of the heart, which is the result of cardiomyocyte death and fibrotic scar formation. The endogenous regenerative capacity of the heart is unable to replenish this significant loss of tissue and conventional medical management cannot correct the underlying defects in cardiac muscle cell number. Recently, tremendous effort is being put into the development of cell transplantation protocol for heart repair, which has been put forward as an alternative therapy to reduce cell damage, cardiomyocyte death and improve tissue contraction. Unfortunately the ideal stem cell population for heart repair has not been identified to date, but several characteristics are defined which the ideal population should have namely, reduce cell damage, reduce cardiomyocyte death, induce differentiation into cardiomyocytes and endothelial cells, and improve tissue contraction. It is unclear whether this will be possible in one optimal population. Therefore the research focus is shifting towards improving the characteristics of the stem cell populations that are identified to date. In this review, we will give an overview of the different stem/progenitor cell populations and their application in cardiac repair and discuss current knowledge on issues like differentiation capacity, paracrine secretion profile, genetic modification of progenitor cells and their influence on cardiac remodeling.
Assuntos
Cardiopatias/cirurgia , Miocárdio/patologia , Medicina Regenerativa , Transplante de Células-Tronco , Células-Tronco , Animais , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Terapia Genética , Cardiopatias/genética , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Miocárdio/metabolismo , Comunicação Parácrina , Recuperação de Função Fisiológica , Regeneração , Células-Tronco/metabolismo , Resultado do Tratamento , Remodelação VentricularRESUMO
BACKGROUND: In recent years, resident cardiac progenitor cells have been identified in, and isolated from the rodent heart. These cells show the potential to form cardiomyocytes, smooth muscle cells, and endothelial cells in vitro and in vivo and could potentially be used as a source for cardiac repair. However, previously described cardiac progenitor cell populations show immature development and need co-culture with neonatal rat cardiomyocytes in order to differentiate in vitro. Here we describe the localisation, isolation, characterisation, and differentiation of cardiomyocyte progenitor cells (CMPCs) isolated from the human heart. METHODS: hCMPCs were identified in human hearts based on Sca-1 expression. These cells were isolated, and FACS, RT-PCR and immunocytochemistry were used to determine their baseline characteristics. Cardiomyogenic differentiation was induced by stimulation with 5-azacytidine. RESULTS: hCMPCs were localised within the atria, atrioventricular region, and epicardial layer of the foetal and adult human heart. In vitro, hCMPCs could be induced to differentiate into cardiomyocytes and formed spontaneously beating aggregates, without the need for co-culture with neonatal cardiomyocytes. CONCLUSION: The human heart harbours a pool of resident cardiomyocyte progenitor cells, which can be expanded and differentiated in vitro. These cells may provide a suitable source for cardiac regeneration cell therapy. (Neth Heart J 2008;16:163-9.).
