间充质干细胞在凋亡过程中释放膜微粒

Mesenchymal Stem Cells Release Membrane Microparticles in the Process of Apoptosis

间充质干细胞(MSC)已经用于多种损伤组织的修复,但无论全身或局部应用,培养的MSC进入体内后短期内大量死亡。为探讨死亡细胞发挥组织修复作用的机制,本研究以大鼠MSC为对象,利用低氧及乏营养为诱导条件,对凋亡MSC释放的亚细胞结构进行了分析。结果表明,低氧(1%O2)及无血清培养均可诱导MSC凋亡,尤以二者联合为著,72 h后细胞凋亡比例达(17.44±2.15)%。与此同时,培养上清经低温超速离心后,流式细胞仪分析证实,细胞可释放大量的膜微粒(microparticles,MP),其表面同时表达CD29、CD44A和凋亡相关的磷脂酰丝氨酸。结论:MSC经诱导后释放MP,其量相当于原细胞数目的15.2倍。MP是组织损伤后细胞间信息传递的重要介质。本研究为探讨MSC治疗机制提供了新的思路。

Though mesenchymal stem cells（MSC） have been clinically used to repair a variety of damaged tissues,the underlying mechanisms remain elusivelely as the majority of the ex vivo expanded MSC die shortly after transplantation.To explore the mechanism in which the death cells play tissue repair effect,apoptosis of rat bone marrow MSC was induced by culturing cells in the conditions of hypoxia or/and serum-free medium,and the subcellular structures in the supernatants were analyzed.The results showed that apoptosis occurred in the presence of either hypoxia or serum-free condition as well,and the apoptotic proportion reached up to（17.44±2.15）% after the cells were treated by hypoxia plus serum free culture for 72 hours.The flow cytometric analysis of the sub-cellular substances harvested by ultracentrifugation of the supernatants found that the MSC released substantial amount of membrane microparticles into the supernatants,which expressed CD29,CD44A and Annexin-Ⅴ-binding phosphatidylserine.It is concluded that the MSC can release membrane microparticles after induction,the amount of these membrane microparticles was around 15-fold of the parent cell numbers.The membrane microparticles is the mediators in the cross-talk between the transplanted cells and their surrounding tissues.This study provides some novel information for the mechanisms of MSC therapy.