Suzuki Etsu, Fujita Daishi, Takahashi Masao, Oba Shigeyoshi, Nishimatsu Hiroaki
Etsu Suzuki, Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki 216-8512, Japan.
World J Stem Cells. 2016 Sep 26;8(9):297-305. doi: 10.4252/wjsc.v8.i9.297.
Mesenchymal stem cells (MSCs) have been used to treat patients suffering from acute myocardial infarction (AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microRNAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease (CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD.
间充质干细胞（MSCs）已被用于治疗急性心肌梗死（AMI）及后续心力衰竭患者。尽管最初认为MSCs可分化为心肌细胞等心脏细胞，但最近的证据表明，MSCs的分化能力极小，注入的MSCs通过旁分泌因子的分泌来恢复心脏功能。MSCs不仅以裸形式分泌旁分泌因子，还通过膜囊泡分泌，包括含有蛋白质、信使RNA和微小RNA等生物活性物质的外泌体。尽管具体细节尚不清楚，但这些生物活性分子在外泌体中被选择性分选，然后以一种受调控的方式从供体细胞释放出来。此外，外泌体通过配体-受体相互作用被受体细胞特异性内化。因此，外泌体是有前景的天然载体，能够稳定且特异性地将生物活性分子转运至受体细胞。事实上，干细胞衍生的外泌体已成功用于动物模型中治疗心血管疾病（CVD），如AMI、中风和肺动脉高压，并且其疗效已得到证实。因此，外泌体给药可能是治疗CVD的一种有前景的策略。此外，对外泌体内容物的修饰可能会增强其治疗效果。未来需要进行临床研究以证实外泌体治疗CVD的疗效。
