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T-Regulatory Cells Confer Increased Myelination and Stem Cell Activity after Stroke-Induced White Matter Injury

1
Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
2
Biomedical Research Concentration, Scholarly Concentrations Program, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(4), 537; https://doi.org/10.3390/jcm8040537
Received: 13 March 2019 / Revised: 5 April 2019 / Accepted: 17 April 2019 / Published: 19 April 2019
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cells in Immunity and Disease)
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Abstract

Stroke-induced hypoxia causes oligodendrocyte death due to inflammation, lack of oxygen and exacerbation of cell death. Bone marrow-derived stem cells (BMSCs) possess an endogenous population of T-regulatory cells (Tregs) which reduce secretion of pro-inflammatory cytokines that lead to secondary cell death. Here, we hypothesize that oligodendrocyte progenitor cells (OPCs) cultured with BMSCs containing their native Treg population show greater cell viability, less pro-inflammatory cytokine secretion and greater myelin production after exposure to oxygen-glucose deprivation and reoxygenation (OGD/R) than OPCs cultured without Tregs. OPCs were cultured and then exposed to OGD/R. BMSCs with or without Tregs were added to the co-culture immediately after ischemia. The Tregs were depleted by running the BMSCs through a column containing a magnetic substrate. Fibroblast growth factor beta (FGF-β) and interleukin 6 (IL-6) ELISAs determined BMSC activity levels. Immunohistochemistry assessed OPC differentiation. OPCs cultured with BMSCs containing their endogenous Tregs showed increased myelin production compared to the BMSCs with depleted Tregs. IL-6 and FGF-β were increased in the group cultured with Tregs. Collectively, these results suggest that BMSCs containing Tregs are more therapeutically active, and that Tregs have beneficial effects on OPCs subjected to ischemia. Tregs play an important role in stem cell therapy and can potentially treat white matter injury post-stroke. View Full-Text
Keywords: bone marrow-derived stem cells; mesenchymal stem cells; T-regulatory cells; white matter injury; stroke; oligodendrocytes; oligodendrocyte precursor cells; oxygen–glucose deprivation; reoxygenation bone marrow-derived stem cells; mesenchymal stem cells; T-regulatory cells; white matter injury; stroke; oligodendrocytes; oligodendrocyte precursor cells; oxygen–glucose deprivation; reoxygenation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Zarriello, S.; Neal, E.G.; Kaneko, Y.; Borlongan, C.V. T-Regulatory Cells Confer Increased Myelination and Stem Cell Activity after Stroke-Induced White Matter Injury. J. Clin. Med. 2019, 8, 537.

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