Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut 06030-1110, USA.
Antioxid Redox Signal. 2009 Aug;11(8):1841-55. doi: 10.1089/ars.2009.2455.
Myocardial ischemia and cardiac dysfunction have been known to follow ischemic heart diseases (IHDs). Despite a plethora of conventional treatment options, their efficacies are associated with skepticism. Cell therapies harbor a promising potential for vascular and cardiac repair, which is corroborated by adequate preclinical evidence. The underlying objectives behind cardiac regenerative therapies subsume enhancing angiomyogenesis in the ischemic myocardium, ameliorating cellular apoptosis, regenerating the damaged myocardium, repopulating the lost resident myocardial cells (smooth muscle, cardiomyocyte, and endothelial cells), and finally, decreasing fibrosis with a consequent reduction in ventricular remodeling. Although-cell based cardiomyoplasty approaches have an immense potential, their clinical utilization is limited owing to the increased need for better candidates for cellular cardiomyoplasty, better routes of delivery, appropriate dose for efficient engraftment, and better preconditioning or genetic-modification strategies for the progenitor and stem cells. Mesenchymal stem cells (MSCs) have emerged as powerful candidates in mediating myocardial repair owing to their unique properties of multipotency, transdifferentiation, intercellular connection with the resident cardiomyocytes via connexin 43 (Cx43)-positive gap junctions in the myocardium, and most important, immunomodulation. In this review, we present an in-depth discussion on the complexities associated with stem and progenitor cell therapies, the potential of preclinical approaches involving MSCs for myocardial repair, and an account of the past milestones and ongoing MSC-based trials in humans.
心肌缺血和心功能障碍已知是缺血性心脏病 (IHD) 的后果。尽管有大量的传统治疗选择，但它们的疗效仍存在争议。细胞疗法为血管和心脏修复提供了有希望的潜力，这一潜力得到了充分的临床前证据的支持。心脏再生疗法的基本目标包括增强缺血心肌中的血管生成、改善细胞凋亡、再生受损的心肌、重新填充丢失的心肌细胞（平滑肌、心肌细胞和内皮细胞），最后，减少纤维化，从而减少心室重构。尽管基于细胞的心肌成形术方法具有巨大的潜力，但由于需要更好的细胞心肌成形术候选物、更好的输送途径、适当的剂量以实现有效的移植、更好的预处理或基因修饰策略用于祖细胞和干细胞，其临床应用受到限制。间充质干细胞 (MSC) 因其多能性、转分化、通过心肌中的间隙连接蛋白 43 (Cx43) 阳性缝隙连接与驻留心肌细胞的细胞间连接的独特特性，以及最重要的免疫调节特性，已成为介导心肌修复的有力候选物。在这篇综述中，我们深入讨论了与干细胞和祖细胞疗法相关的复杂性、涉及 MSC 的临床前方法在心肌修复中的潜力，以及过去的里程碑和正在进行的基于 MSC 的人体试验的情况。
