Regulatory T-cells within bone marrow-derived stem cells actively confer immunomodulatory and neuroprotective effects against stroke
| Autor: | Cesario V. Borlongan, Sandra Acosta, Xunming Ji, Elliot G. Neal, Yuji Kaneko |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Population chemical and pharmacologic phenomena Inflammation Adaptive Immunity Mesenchymal Stem Cell Transplantation T-Lymphocytes Regulatory Neuroprotection Brain Ischemia Immunomodulation 03 medical and health sciences 0302 clinical medicine stomatognathic system immune system diseases Animals Humans Medicine IL-2 receptor education Cells Cultured education.field_of_study business.industry FOXP3 Mesenchymal Stem Cells hemic and immune systems Original Articles Rats Mice Inbred C57BL Stroke Transplantation medicine.anatomical_structure Neurology Cancer research Cytokines Neurology (clinical) Bone marrow medicine.symptom Stem cell Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Zdroj: | J Cereb Blood Flow Metab |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1177/0271678x18766172 |
| Popis: | Regulatory T-cells (Tregs) may exert a neuroprotective effect on ischemic stroke by inhibiting both inflammation and effector T-cell activation. Transplantation of human bone marrow-derived stem cells (BMSCs) in ischemic stroke affords neuroprotection that results in part from the cells’ anti-inflammatory property. However, the relationship between Tregs and BMSCs in treatment of ischemic stroke has not been fully elucidated. Here, we tested the hypothesis that Tregs within the BMSCs represent active mediators of immunomodulation and neuroprotection in experimental stroke. Primary rat neuronal cells were subjected to an oxygen-glucose deprivation and reperfusion (OGD/R) condition. The cells were re-perfused and co-cultured with Tregs and/or BMSCs. We detected a minority population of Tregs within BMSCs with both immunocytochemistry (ICC) and flow cytometry identifying cells expressing phenotypic markers of CD4, CD25, and FoxP3 protein. BMSCs with the native population of Tregs conferred maximal neuroprotection compared to the treatment conditions containing 0%, 10%, and 100% relative ratio Tregs. Increasing the Treg population resulted in increased IL6 secretion and decreased FGF-β secretion by BMSCs. This study shows that a minority population of Tregs exists within the therapeutic BMSC population, which serves as robust mediators of the immunomodulatory and neuroprotective effect provided by BMSC transplantation. |
| Databáze: | OpenAIRE |
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