T-Regulatory Cells Confer Increased Myelination and Stem Cell Activity after Stroke-Induced White Matter Injury
Open Access
- 19 April 2019
- journal article
- research article
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 8 (4), 537
- https://doi.org/10.3390/jcm8040537
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.Keywords
Funding Information
- National Institutes of Health (R01 NS071956, R01 NS090962, R21 NS089851, R21 NS094087)
- U.S. Department of Veterans Affairs (I01 BX001407)
This publication has 52 references indexed in Scilit:
- The immunology of acute strokeNature Reviews Neurology, 2012
- Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury ModelPLOS ONE, 2012
- Regulatory T Cells Enhance Mast Cell Production of IL-6 via Surface-Bound TGF-βThe Journal of Immunology, 2012
- The great migration of bone marrow-derived stem cells toward the ischemic brain: Therapeutic implications for stroke and other neurological disordersProgress in Neurobiology, 2011
- Tissue plasminogen activator prevents white matter damage following strokeThe Journal of Experimental Medicine, 2011
- Inflammatory mechanisms in ischemic stroke: role of inflammatory cellsJournal of Leukocyte Biology, 2010
- Bone Marrow Stromal Cells Increase Oligodendrogenesis after StrokeJournal of Cerebral Blood Flow & Metabolism, 2009
- Molecular targets in cerebral ischemia for developing novel therapeuticsBrain Research Reviews, 2007
- Soluble Interleukin-6 (IL-6) Receptor/IL-6 Fusion Protein Enhances in Vitro Differentiation of Purified Rat Oligodendroglial Lineage CellsMolecular and Cellular Neuroscience, 2002
- The Risk of Gastrointestinal and other Primary Malignant Diseases Following Gastric CancerActa Oncologica, 1991