Assessment of Enrichment of Human Mesenchymal Stem Cells Based on Plasma and Mitochondrial Membrane Potentials
- 1 March 2020
- journal article
- research article
- Published by Mary Ann Liebert Inc in Bioelectricity
- Vol. 2 (1), 21-32
- https://doi.org/10.1089/bioe.2019.0024
Abstract
Background: Human mesenchymal stem cells (hMSCs) are utilized preclinically and clinically as a candidate cell therapy for a wide range of inflammatory and degenerative diseases. Despite promising results in early clinical trials, consistent outcomes with hMSC-based therapies have proven elusive in many of these applications. In this work, we attempt to address this limitation through the design of a stem cell therapy to enrich hMSCs for desired electrical and ionic properties with enhanced stemness and immunomodulatory/regenerative capacity. Materials and Methods: In this study, we sought to develop initial protocols to achieve electrically enriched hMSCs (EE-hMSCs) with distinct electrical states and assess the potential relationship with respect to hMSC state and function. We sorted hMSCs based on fluorescence intensity of tetramethylrhodamine ethyl ester (TMRE) and investigated phenotypic differences between the sorted populations. Results: Subpopulations of EE-hMSCs exhibit differential expression of genes associated with senescence, stemness, immunomodulation, and autophagy. EE-hMSCs with low levels of TMRE, indicative of depolarized membrane potential, have reduced mRNA expression of senescence-associated markers, and increased mRNA expression of autophagy and immunomodulatory markers relative to EE-hMSCs with high levels of TMRE (hyperpolarized). Conclusions: This work suggests that the utilization of EE-hMSCs may provide a novel strategy for cell therapies, enabling live cell enrichment for distinct phenotypes that can be exploited for different therapeutic outcomes.This publication has 113 references indexed in Scilit:
- Quantitative measurement of mitochondrial membrane potential in cultured cells: calcium‐induced de‐ and hyperpolarization of neuronal mitochondriaJournal Of Physiology-London, 2012
- Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept studyThe Lancet Neurology, 2012
- Molecular Mechanism for Adiponectin-dependent M2 Macrophage PolarizationOnline Journal of Public Health Informatics, 2011
- Factors affecting mesenchymal stromal cells yield from bone marrow aspirationChinese Journal of Cancer Research, 2011
- A link between the accumulation of DNA damage and loss of multi‐potency of human mesenchymal stromal cellsJournal of Cellular and Molecular Medicine, 2010
- Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory propertiesProceedings of the National Academy of Sciences of the United States of America, 2010
- Astrocytic endfoot Ca 2+ and BK channels determine both arteriolar dilation and constrictionProceedings of the National Academy of Sciences of the United States of America, 2010
- A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of Intravenous Adult Human Mesenchymal Stem Cells (Prochymal) After Acute Myocardial InfarctionJournal of the American College of Cardiology, 2009
- Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 productionNature Medicine, 2008
- Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem CellsOnline Journal of Public Health Informatics, 2008