Spontaneous apoptosis of cells in therapeutic stem cell preparation exert immunomodulatory effects through release of phosphatidylserine

查看全文 作　　者：Xuemei [1,2]He;Weiqi [1]Hong;Jingyun [1]Yang;Hong [1]Lei;Tianqi [1]Lu;Cai [1]He;Zhenfei [1]Bi;Xiangyu [1]Pan;Yu [1]Liu;Lunzhi [1]Dai;Wei [1]Wang;Canhua [1]Huang;Hongxin [1]Deng;Xiawei [1]Wei

机构地区：[1]Laboratory of Aging Research and Cancer Drug Target,State Key Laboratory of Biotherapy and Cancer Center,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu,Sichuan,People’s Republic of China;[2]Experimental Medicine Center,the Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan,People’s Republic of China

出　　处：《Signal Transduction and Targeted Therapy》索引2021年第6卷第8期,共14页

基　　金：This work was supported by the National Natural Science Foundation Regional Innovation and Development(number U19A2003);National Major Scientific and Technological Special Project for'Significant New Drugs Development”(number 2018ZX09733001);Excellent Youth Foundation of the Sichuan Scientific Committee Grant in China(number 2019JDJQ008);Development Program of China(number 2016YFA0201402);the National Natural Science Foundation of China(number 81800421);the National Natural Science Foundation of China(number 81821002). 摘　　要：Mesenchymal stem cell(MSC)-mediated immunomodulation has been harnessed for the treatment of human diseases,but its underlying mechanism has not been fully understood.Dead cells,including apoptotic cells have immunomodulatory properties.It has been repeatedly reported that the proportion of nonviable MSCs in a MSC therapeutic preparation varied from 5-50%in the ongoing clinical trials.It is conceivable that the nonviable cells in a MSC therapeutic preparation may play a role in the therapeutic effects of MSCs.We found that the MSC therapeutic preparation in the present study had about 5%dead MSCs(DMSCs),characterized by apoptotic cells.Namely,1×10^(6) MSCs in the preparation contained about 5×10^(4) DMSCs.We found that the treatment with even 5×10^(4) DMSCs alone had the equal therapeutic effects as with 1×10^(6) MSCs.This protective effect of the dead MSCs alone was confirmed in four mouse models,including concanavalin A(ConA)-and carbon tetrachloride(CCI4)-induced acute liver injury,LPS-induced lung injury and spinal cord injury.We also found that the infused MSCs died by apoptosis in vivo.Furthermore,the therapeutic effect was attributed to the elevated level of phosphatidylserine(PS)upon the injection of MSCs or DMSCs.The direct administration of PS liposomes(PSLs)mimic apoptotic cell fragments also exerted the protective effects as MSCs and DMSCs.The Mer tyrosine kinase(MerTK)deficiency or the knockout of chemokine receptor C-C motif chemokine receptor 2(CCR2)reversed these protective effects of MSCs or DMSCs.These results revealed that DMSCs alone in the therapeutic stem cell preparation or the apoptotic cells induced in vivo may exert the same immunomodulatory property as the'living MSCs preparation'through releasing PS,which was further recognized by MerTK and participated in modulating immune cells. 关键词：THERAPEUTIC protective PREPARATION

相关文献

参考文献（57）
引证文献（8）
耦合文献（12）

参考文献(57)

引证文献(8)

耦合文献(12)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

Spontaneous apoptosis of cells in therapeutic stem cell preparation exert immunomodulatory effects through release of phosphatidylserine

参考文献(57)

引证文献(8)

耦合文献(12)

用户提示