| IntroductionStudies show that mature cardiomyocytes don't have the capability of regeneration. When a MI occurs, the cardiac muscles within the affected area can only get the regenerated non-contractile scar tissues through fiber tissues, which lead to mal-efficient cardiac function. Clinically there is no radical treatment to regenerate and rebuild the stricken coronary artery and the infarcted myocardium. To meet the need, the cellular replacement therapy becomes an ideal treatment to fill up this blank area. Large number of studies prove that cardiac function can be improved after MI with the in-transplantation of embryonic cardiomyocytes, neonatal cardiomyocytes, embryonic stem cells, skeletal myoblasts cells, bone marrow hematopoietic side-population stem cells (SP) and mesenchymal stem cells (MSCs). Autologous marrow mesenchymal stem cells have much greater advantage than others because that they are easy to obtain, that they have no immunosuppression, have multi differentiating potential, have moral support and have no tumor inducing possibilities. In recent years, we have done some research work on the plasticity of adult MSCs and its application in myocardial regenerative medicine, including differentiation of MSCs into cardiomyocytes in vitro and in vivo. We hope these could be promissing for the future using human adult stem cells ontherapeutic cardiomyoplasty. Methods and ResultsFirstly, we investigated the potential of the adult rat or human bone marrow MSCs in in vitro cardiomyogenic differentiation in vitro. MSCs were cultured in medium supplemented with 5-azacytidine for cardiamyocyte differentiation.Immunohistochemiscal analysis revealed that induced cells expressed desmin, GATA4, cTnI (cardiac Tropnin I) and connexin43. MyHC(Myosin Heavy Chain) gene were also detected by RT-PCR technique. Electron microscopy showed a centrally positioned nucleus and cytoplasmic myofilaments. Such induced muscle cells exhibited cardiac-like electrophysiological properties including voltage-sensitve ionic current Ina and Ik. These findings suggested that purified hMSCs from adult bone marrow can be induced to differentiatted into functional cardiac-like muscle cells in vitro and might be an alternative source of undifferentiated cells for cell therapy in myocardial regeneration.On the basis of in vitro experimental data, we demonstrated the possibility of survival, migratory and differentiation of rat MSCs in chronic infarcted myocardium. The models of injured hearts were induced by left coronary artery ligation. 4 W after mrocardial infarction, 2X106 rMSCs were transplanted into each host heart and 4 weeks later the cellular transplanted hearts were harvested and investigated. Results revealed that the DAPI-labelled rMSCs with oval nucleus were broadly distributed and their distributions were parallel with the host myocardium fibers of the infarcted host hearts. These cells stained positively for cardiac specific protein. These data suggest that the transplanted adult MSCs were subject to local differentiation environmental signals. Evidently the purified exogenous rMSCs can survive and site-defferentiared into cardiomyocytes in chronic infracted hearts. Entering a new microenvironment, adult stem cells might be affected by the adjacent differentiating cells to process genetical reprogramming, which resulted in generation of different cell types. It might be true that the microenvironment has important implications for the fate ofstem and precursor cells. As we all know, once the myocardial infarction develops there is a rapid onset of contraction band necrosis and an intense inflammatory cascade. By means of transplanting DAPI-labeled MSCs into injured hearts at different time after myocardial infarction, we intensively investigated the optimal time for transplantation from aspects of cell biology, histology, immunohistochemistry and functional analysis. We found that few engrafted cells survived when grafted 1 week after MI since the inflammatory reaction, wh...
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