Golpanian Samuel, Wolf Ariel, Hatzistergos Konstantinos E, Hare Joshua M
Interdisciplinary Stem Cell Institute, Department of Medicine, and Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Physiol Rev. 2016 Jul;96(3):1127-68. doi: 10.1152/physrev.00019.2015.
Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise. Numerous preclinical studies of ischemic and nonischemic cardiomyopathy employing MSC-based therapy have demonstrated that the properties of reducing fibrosis, stimulating angiogenesis, and cardiomyogenesis have led to improvements in the structure and function of remodeled ventricles. Further attempts have been made to augment MSCs' effects through genetic modification and cell preconditioning. Progression of MSC therapy to early clinical trials has supported their role in improving cardiac structure and function, functional capacity, and patient quality of life. Emerging data have supported larger clinical trials that have been either completed or are currently underway. Mechanistically, MSC therapy is thought to benefit the heart by stimulating innate anti-fibrotic and regenerative responses. The mechanisms of action involve paracrine signaling, cell-cell interactions, and fusion with resident cells. Trans-differentiation of MSCs to bona fide cardiomyocytes and coronary vessels is also thought to occur, although at a nonphysiological level. Recently, MSC-based tissue engineering for cardiovascular disease has been examined with quite encouraging results. This review discusses MSCs from their basic biological characteristics to their role as a promising therapeutic strategy for clinical cardiovascular disease.
间充质干细胞（MSCs）是广泛分布的细胞，具有出生后自我更新和多向分化的能力。MSCs能逃避免疫检测，分泌一系列抗炎和抗纤维化介质，并且非常重要的是能激活内源性前体细胞。这些特性构成了基于细胞的疗法用于治疗炎症和纤维化疾病的临床应用策略的基础。在心血管医学中，对缺血性和非缺血性心肌病患者施用自体或异体MSCs具有重大前景。许多采用基于MSCs治疗的缺血性和非缺血性心肌病的临床前研究表明，其减少纤维化、刺激血管生成和心肌生成的特性已导致重塑心室的结构和功能得到改善。人们还进一步尝试通过基因改造和细胞预处理来增强MSCs的作用。MSCs治疗进展到早期临床试验已证实其在改善心脏结构和功能、功能能力及患者生活质量方面的作用。新出现的数据支持了已完成或正在进行的更大规模的临床试验。从机制上讲，MSCs治疗被认为通过刺激先天性抗纤维化和再生反应而使心脏受益。其作用机制涉及旁分泌信号传导、细胞间相互作用以及与内源性细胞融合。尽管处于非生理水平，但也认为MSCs可转分化为真正的心肌细胞和冠状血管。最近，基于MSCs的心血管疾病组织工程研究已取得相当令人鼓舞的结果。本综述讨论了MSCs从其基本生物学特性到其作为临床心血管疾病有前景的治疗策略的作用。
