Uterine Immunoprivileged Cells Restore Cardiac Function of Male Recipients After Myocardial Infarction

主要组织相容性复合体 MHC I级 CD8型 免疫学 生物 细胞毒性T细胞 移植 MHC II级 医学 内科学 免疫系统 体外 遗传学
作者
Zexu Peng,Ana Lüdke,Jun Wu,Shuhong Li,Faisal J. Alibhai,Yichong Zhang,Yunfei Fan,Huifang Song,Sheng He,Jun Xie,Ren‐Ke Li
出处
期刊:Stem Cells [Wiley]
卷期号:42 (5): 430-444
标识
DOI:10.1093/stmcls/sxae008
摘要

It has been documented that the uterus plays a key cardio-protective role in pre-menopausal women, which is supported by uterine cell therapy, to preserve cardiac functioning post-myocardial infarction, being effective among females. However, whether such therapies would also be beneficial among males is still largely unknown. In this study, we aimed to fill in this gap in knowledge by examining the effects of transplanted uterine cells on infarcted male hearts. We identified, based on major histocompatibility complex class I (MHC-I) expression levels, 3 uterine reparative cell populations: MHC-I(neg), MHC-I(mix), and MHC-I(pos). In vitro, MHC-I(neg) cells showed higher levels of pro-angiogenic, pro-survival, and anti-inflammatory factors, compared to MHC-I(mix) and MHC-I(pos). Furthermore, when cocultured with allogeneic mixed leukocytes, MHC-I(neg) had lower cytotoxicity and leukocyte proliferation. In particular, CD8+ cytotoxic T cells significantly decreased, while CD4+CD25+ Tregs and CD4-CD8- double-negative T cells significantly increased when cocultured with MHC-I(neg), compared to MHC-I(mix) and MHC-I(pos) cocultures. In vivo, MHC-I(neg) as well as MHC-I(mix) were found under both syngeneic and allogeneic transplantation in infarcted male hearts, to significantly improve cardiac function and reduce the scar size, via promoting angiogenesis in the infarcted area. All of these findings thus support the view that males could also benefit from the cardio-protective effects observed among females, via cell therapy approaches involving the transplantation of immuno-privileged uterine reparative cells in infarcted hearts.

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