Human endometrium-derived stem cell improves cardiac function after myocardial ischemic injury by enhancing angiogenesis and myocardial metabolism

Stem Cell Research & Therapy

Lingxia Zhao¹  Sanyuan Zhang²  Changping Yan²  Hongliang Wang³  Wenjuan Yin⁴  Jie Zhang⁴  Xiangying Jiao⁴  Xiaoyan Zhai⁴  Jun Xie⁴  Hui Gong⁴  Huifang Song⁴  Zexu Peng⁴  Xuemei Fan⁵  Kun Yang⁵  Sheng He⁶  Yi Ping⁷  Ren-Ke Li⁸ 

[1] Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, The Third Hospital of Shanxi Medical University, Taiyuan, China;The First Hospital of Shanxi Medical University, Taiyuan, China;The First Hospital of Shanxi Medical University, Taiyuan, China;Key Laboratory of Molecular Imaging, Molecular Imaging Precision Medicine Collaborative Innovation Center, Shanxi Medical University, Taiyuan, China;The Laboratory of Stem Cell Regenerative Medicine Research, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Cell Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China;The Laboratory of Stem Cell Regenerative Medicine Research, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Cell Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China;Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, The Third Hospital of Shanxi Medical University, Taiyuan, China;The Laboratory of Stem Cell Regenerative Medicine Research, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Cell Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China;The First Hospital of Shanxi Medical University, Taiyuan, China;The Second Hospital of Shanxi Medical University, Taiyuan, China;Toronto General Hospital Research Institute, University Health Network, Toronto, Canada;

关键词: Human endometrium-derived stem cells;    Myocardial ischemic injury;    Human bone marrow mesenchymal stem cells;    Angiogenesis;    Cardiac repair;   

DOI  :  10.1186/s13287-021-02423-5

来源: Springer

【 摘 要 】

BackgroundThe human endometrium in premenopausal women is an active site of physiological angiogenesis, with regenerative cells present, suggesting that the endometrium contains adult angiogenic stem cells. In the context of cardiac repair after ischemic injury, angiogenesis is a crucial process to rescue cardiomyocytes. We therefore investigated whether human endometrium-derived stem cells (hEMSCs) can be used for cardiac repair after ischemic injury and their possible underlying mechanisms.MethodsComparisons were made between hEMSCs successfully isolated from 22 premenopausal women and human bone marrow mesenchymal stem cells (hBMSCs) derived from 25 age-matched patients. Cell proliferation, migration, differentiation, and angiogenesis were evaluated through in vitro experiments, while the ability of hEMSCs to restore cardiac function was examined by in vivo cell transplantation into the infarcted nude rat hearts.ResultsIn vitro data showed that hEMSCs had greater proliferative and migratory capacities, whereas hBMSCs had better adipogenic differentiation ability. Human umbilical cord vein endothelial cells, treated with conditioned medium from hEMSCs, had significantly higher tube formation than that from hBMSCs or control medium, indicating greater angiogenic potentials for hEMSCs. In vivo, hEMSC transplantation preserved cardiac function, decreased infarct size, and improved tissue repair post-injury. Cardiac metabolism, assessed by 18F-FDG uptake, showed that 18F-FDG uptake at the infarction area was significantly higher in both hBMSC and hEMSC groups, compared to the PBS control group, with hEMSCs having the highest uptake, suggesting hEMSC treatment improves cardiomyocyte metabolism and survival after injury. Mechanistic assessment of the angiogenic potential for hEMSCS revealed that angiogenesis-related factors angiopoietin 2, Fms-like tyrosine kinase 1, and FGF9 were significantly upregulated in hEMSC-implanted infarcted hearts, compared to the PBS control group.ConclusionhEMSCs, compared to hBMSCs, have greater capacity to induce angiogenesis, and improved cardiac function after ischemic injury.

【 授权许可】

CC BY