4.7 Article

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

Journal

STEM CELL RESEARCH & THERAPY
Volume 12, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13287-021-02423-5

Keywords

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

Funding

  1. National Natural Science Foundation of China [81702239, 81900274]
  2. Natural Science Foundation for Young Scientists of Shanxi Province [201701D221252]
  3. Key R&D program of Shanxi Province [201903D421023]
  4. Fund for Shanxi Key Subjects Construction, FSKSC
  5. Fund for Shanxi 1331 Project Key Subjects Construction

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Human endometrium-derived stem cells (hEMSCs) exhibit enhanced capacities for cell proliferation and migration, as well as greater angiogenic potentials, contributing to improved cardiac repair post ischemic injury in comparison to human bone marrow mesenchymal stem cells (hBMSCs).
Background The 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. Methods Comparisons 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. Results In 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 F-18-FDG uptake, showed that F-18-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. Conclusion hEMSCs, compared to hBMSCs, have greater capacity to induce angiogenesis, and improved cardiac function after ischemic injury.

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