Suppressing Pyroptosis Augments Post-Transplant Survival of Stem Cells and Cardiac Function Following Ischemic Injury

International Journal of Molecular Sciences

Jiyun Lee¹  Hyang-Hee Seo¹  Gyoonhee Han²  Jun-Hee Park²  Chang Youn Lee²  Sunhye Shin²  Jung-Won Choi³  Soyeon Lim³  Byeong-Wook Song³  Seongtae Jeong³  Seahyoung Lee³  Ki-Chul Hwang³  Il-Kwon Kim³  Sang Woo Kim³ 

[1] Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea;Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul 03722, Korea;Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si 25601, Korea;

关键词: pyroptosis;    M1 macrophage;    stem cells;    miR-762;    I/R injury;   

DOI  :  10.3390/ijms22157946

来源: DOAJ

【 摘 要 】

The acute demise of stem cells following transplantation significantly compromises the efficacy of stem cell-based cell therapeutics for infarcted hearts. As the stem cells transplanted into the damaged heart are readily exposed to the hostile environment, it can be assumed that the acute death of the transplanted stem cells is also inflicted by the same environmental cues that caused massive death of the host cardiac cells. Pyroptosis, a highly inflammatory form of programmed cell death, has been added to the list of important cell death mechanisms in the damaged heart. However, unlike the well-established cell death mechanisms such as necrosis or apoptosis, the exact role and significance of pyroptosis in the acute death of transplanted stem cells have not been explored in depth. In the present study, we found that M1 macrophages mediate the pyroptosis in the ischemia/reperfusion (I/R) injured hearts and identified miRNA-762 as an important regulator of interleukin 1β production and subsequent pyroptosis. Delivery of exogenous miRNA-762 prior to transplantation significantly increased the post-transplant survival of stem cells and also significantly ameliorated cardiac fibrosis and heart functions following I/R injury. Our data strongly suggest that suppressing pyroptosis can be an effective adjuvant strategy to enhance the efficacy of stem cell-based therapeutics for diseased hearts.

【 授权许可】

Unknown