Mechanisms of bone marrow stem cells for myocardial repair

尽管细胞疗法作为一种新的治疗心力衰竭的策略显示出巨大的希望，但其确切的机制尚不清楚。此外，细胞疗法相对于传统细胞因子疗法的优势还有待阐明。本研究旨在比较细胞治疗和细胞因子治疗对缺血性和非缺血性心力衰竭实验模型的功能改善。结扎左前降支诱导小鼠缺血性心衰，腹腔注射阿霉素诱导小鼠非缺血性心衰。建立心力衰竭模型后，随机给予小鼠心肌内单次注射2x10^5 c-kit阳性骨髓干细胞（细胞治疗）、肝生长因子（细胞因子治疗）或PBS注射（对照组）。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，减少缺血心肌纤维化面积，从而显著提高小鼠存活率，增强心功能（与对照组相比p<0.05）。在非缺血性心力衰竭模型中，细胞治疗显著提高了存活率和心功能（与对照组相比p<0.05），而细胞因子治疗没有显著提高，尽管细胞因子治疗抑制了心肌细胞的纤维化和凋亡。细胞治疗和细胞因子治疗都是缺血性心力衰竭的替代治疗方法。然而，细胞疗法对非缺血性心力衰竭的治疗比单一生长因子的细胞因子治疗更有效。

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.