Donor MSCs release apoptotic bodies to improve myocardial infarction via autophagy regulation in recipient cells

作者：Huan Liu, Siying Liu, Xinyu Qiu, Xinyu Qiu, Xiaoshan Yang, Lili Bao, Fengxing Pu, Congye Li, Congye Li, Kun Xuan, Jun Zhou, Zhihong Deng, Shiyu Liu, Shiyu Liu, Yan Jin · 发表于：Autophagy · 年份：2020 · DOI：10.1080/15548627.2020.1717128 · 被引用次数：228 · 研究领域：Autophagy in Disease and Therapy、Extracellular vesicles in disease、Mesenchymal stem cell research

Mesenchymal stem cell (MSC) transplantation has been widely applied as a potential therapeutic for multiple diseases. However, the underlying therapeutic mechanisms are not fully understood, especially the paradox between the low survival rate of transplanted cells and the beneficial therapeutic effects generated by these cells. Herein, in a myocardial infarction (MI) model, we found that transplanted MSCs released apoptotic bodies (ABs) to enhance angiogenesis and improve cardiac functional reclovery via regulating macroautophagy/autophagy in the recipient endothelial cells (ECs). Mechanistically, after local transplantation, MSCs underwent extensive apoptosis in the short term and released ABs, which were engulfed by the recipient ECs. Then, in the ECs, ABs activated lysosome functions and promoted the expression of TFEB (transcription factor EB), which is a master gene in lysosomal biogenesis and autophagy. Finally, the increase in TFEB enhanced autophagy-related gene expression in ECs and promoted angiogenesis and cardiac functional recovery after MI. Collectively, we found that apoptotic donor MSCs promote angiogenesis via regulating autophagy in the recipient ECs, unveiling the role of donor cell apoptosis in the therapeutic effects generated by cell transplantation.Abbreviations: 3-MA: 3-methyladenine; ABs: apoptotic bodies; BECN1: beclin 1; CASP3: caspase 3; CQ: chloroquine; ECs: endothelial cells; EVs: extracellular vesicles; LAMP1: lysosomal-associated membrane prot...