Suppressing pyroptosis augments post‐transplant survival of stem cells and cardiac function following ischemic injury

Chang Youn Lee, Seahyoung Lee, Seongtae Jeong, Jiyun Lee, Hyang Hee Seo, Sunhye Shin, Jun Hee Park, Byeong Wook Song, Il Kwon Kim, Jung Won Choi, Sang Woo Kim, Gyoonhee Han, Soyeon Lim, Ki Chul Hwang

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Abstract

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. How-ever, 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 ische-mia/reperfusion (I/R) injured hearts and identified miRNA‐762 as an important regulator of inter-leukin 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.

Original languageEnglish
Article number7946
JournalInternational journal of molecular sciences
Volume22
Issue number15
DOIs
Publication statusPublished - 2021 Aug 1

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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