4.6 Article

Mitochondrial Membrane Potential Identifies a Subpopulation of Mesenchymal Progenitor Cells to Promote Angiogenesis and Myocardial Repair

Journal

CELLS
Volume 11, Issue 10, Pages -

Publisher

MDPI
DOI: 10.3390/cells11101713

Keywords

mitochondrial membrane potential; mesenchymal progenitor cells; cytokine; angiogenesis; myocardial infarction; heart failure

Categories

Funding

  1. NIH [R01HL114951]
  2. AHA Transformational Project Award [18TPA34170188]
  3. Ohio State University startup fund

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A subpopulation of human mesenchymal progenitor cells (hMPCs) sorted based on low mitochondrial membrane potential exhibit enhanced stemness and survival capacity, which could serve as a potential donor cell source for cellular therapy for ischemic heart disease.
Identifying effective donor cells is one of obstacles that limits cell therapy for heart disease. In this study, we sorted a subpopulation of human mesenchymal progenitor cells (hMPCs) from the right atrial appendage using the low mitochondrial membrane potential. Compared to the non-sorted cells, hMPCs hold the capacity for stemness and enrich mesenchymal stem cell markers. The hMPCs display better ability for survival, faster proliferation, less production of reactive oxygen species (ROS), and greater release of cytoprotective cytokines. The hMPCs exhibit decreased expression of senescence genes and increased expression of anti-apoptotic and antioxidant genes. Intramyocardial injection of hMPCs into the infarcted heart resulted in increased left ventricular ejection fraction and reduced cardiac remodeling and infarct size in the group of animals receiving hMPCs. Both in vitro and in vivo studies indicated hMPCs have the potential to differentiate into endothelial cells and smooth muscle cells. Immunohistochemistry staining showed that cell therapy with hMPCs enhances cardiac vascular regeneration and cardiac proliferation, and decreases cardiac cell apoptosis, which is associated with the increased secretion of cytoprotective and pro-angiogenic cytokines. Overall, we discovered a subpopulation of human mesenchymal progenitor cells via their low mitochondrial membrane potential, which might provide an alternative donor cell source for cellular therapy for ischemic heart disease.

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