Hypoxic preconditioned aged BMSCs accelerates MI injury repair by modulating inflammation, oxidative stress and apoptosis

Huifang Song; Bin Li; Rui Guo; Sheng He; Zexu Peng; Junyuan Qu; Yunhe Zhao; Xiaoyan Zhai; Wenjuan Yin; Kun Yang; Xuemei Fan; Jie Zhang; Jiayin Tan; Yang Liu; Jun Xie; Jun Xu

doi:10.1016/j.bbrc.2022.08.039

Hypoxic preconditioned aged BMSCs accelerates MI injury repair by modulating inflammation, oxidative stress and apoptosis

Biochem Biophys Res Commun. 2022 Oct 30:627:45-51. doi: 10.1016/j.bbrc.2022.08.039. Epub 2022 Aug 17.

Authors

Huifang Song¹, Bin Li², Rui Guo³, Sheng He⁴, Zexu Peng⁴, Junyuan Qu³, Yunhe Zhao², Xiaoyan Zhai⁴, Wenjuan Yin⁴, Kun Yang⁴, Xuemei Fan⁴, Jie Zhang⁴, Jiayin Tan², Yang Liu², Jun Xie⁵, Jun Xu⁶

Affiliations

¹ Department of Hepatological Surgery, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Anatomy, Shanxi Medical University, Taiyuan, China; Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, China. Electronic address: songhuifang0111@yeah.net.
² Department of Anatomy, Shanxi Medical University, Taiyuan, China.
³ Department of Pathology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
⁴ Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, China.
⁵ Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, China. Electronic address: junxie@sxmu.edu.cn.
⁶ Department of Hepatological Surgery, First Hospital of Shanxi Medical University, Taiyuan, China. Electronic address: Junxuty@163.com.

PMID: 36007334
DOI: 10.1016/j.bbrc.2022.08.039

Abstract

The benefits of autologous cell therapy for cardiac repair are diminished in aged individuals due to the limited quality and poor tolerance of aged stem cells in the ischemic micro-environment. The safe and efficient methods to improve the therapeutic effect of aged stem cells are needed to treat the increasing number of aged patients with cardiac diseases. In the present study, we aimed to determine whether hypoxic preconditioning can improve the therapeutic effect of aged stem cells even if the responsiveness of aged MSCs is poor, and to seek the underlying mechanism. Using a murine model of MI, our results showed that hypoxic preconditioning promoted the therapeutic effect of aged BMSCs, which was expressed in improved cardiac function, decreased scar size and alleviated cardiac remodeling in vivo. This in vivo effect of hypoxic preconditioned aged BMSCs was associated with alleviated inflammation, oxidative stress and apoptosis in infarcted heart. In vitro studies confirmed that hypoxic preconditioned aged BMSCs exert cytoprotective impacts on H9C2 cells against lethal hypoxia injury via attenuating oxidative stress and apoptosis. Our data support the promise of hypoxic preconditioning as a potential strategy to improve autologous stem cell therapy for ischemic heart injury in aged individuals.

Keywords: Aged BMSCs; Apoptosis; Hypoxic preconditioning; Inflammation; Myocardial infarction; Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Animals
Apoptosis
Humans
Hypoxia
Inflammation / therapy
Mesenchymal Stem Cell Transplantation* / methods
Mesenchymal Stem Cells*
Mice
Myocardial Infarction* / therapy
Oxidative Stress