Mechanisms of bone marrow stem cells for myocardial repair

虽然细胞疗法作为心力衰竭的新治疗策略显示出巨大的前景，但其确切机制仍不清楚。此外，细胞疗法相对于常规细胞因子疗法的优势还有待阐明。本研究旨在比较细胞疗法和细胞因子疗法在缺血性和非缺血性心力衰竭实验模型中实现的功能改善。结扎小鼠左前降支造成缺血性心力衰竭，腹腔注射阿霉素造成非缺血性心力衰竭。在建立心力衰竭模型后，小鼠被随机给予2x10^5 c-kit阳性骨髓干细胞（细胞疗法）、肝生长因子（细胞因子疗法）或仅PBS注射液（对照）的单次心肌内注射。在缺血性心力衰竭模型中，细胞治疗和细胞因子治疗均能显著增加缺血心肌血管密度，抑制心肌细胞凋亡，缩小缺血心肌纤维化面积，从而显著提高小鼠存活率和增强心功能（p<0.05 vs对照治疗）。在非缺血性心力衰竭模型中，通过细胞治疗实现了存活率和心脏功能的显著增加（p<0.05 vs对照治疗），但通过细胞因子治疗没有实现，尽管细胞因子治疗抑制了心肌细胞的纤维化和凋亡。细胞疗法和细胞因子疗法都是缺血性心力衰竭的替代疗法。然而，细胞疗法对于治疗非缺血性心力衰竭比通过施用单一生长因子实现的细胞因子疗法更有效。

Although cell therapy shows great promise as a new therapeutic strategy for heart failure, its precise mechanisms remain unclear. Furthermore, the advantages of cell therapy over conventional cytokine therapy have yet to be clarified. This study was designed to compare the functional improvement achieved by cell therapy and cytokine therapy in both ischemic and non-ischemic heart failure experimental models. Ischemic heart failure was induced by ligating the left anterior descending artery, and non-ischemic heart failure was induced by an intraperitoneal injection of doxorubicin, respectively, in mice. After establishing the heart failure models, mice were randomly given a single intramyocardial injection of 2x10^5 c-kit-positive bone marrow stem cells (cell therapy), hepatic growth factor (cytokine therapy), or PBS injection only (control). In the ischemic heart failure model, both cell therapy and cytokine therapy increased the vessel density significantly, inhibited apoptosis of myocytes, and decreased the fibrotic area in the ischemic myocardium, which resulted in a significant increase in the survival rate and enhancement of the cardiac function of these mice (p<0.05 vs control therapy). In the non-ischemic heart failure model, significant increases in the survival rate and cardiac function were achieved by cell therapy (p<0.05 vs control therapy), but not by cytokine therapy, although cytokine therapy inhibited the fibrosis and apoptosis of the cardiomyocytes. Both cell therapy and cytokine therapy are alternative treatments for ischemic heart failure. However, cell therapy is more effective for the treatment of non-ischemic heart failure than cytokine therapy achieved by the administration of a single growth factor.