Regulatory T-cells within bone marrow-derived stem cells actively confer immunomodulatory and neuroprotective effects against stroke

Abstract

Regulatory T-cells (T) 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 T and BMSCs in treatment of ischemic stroke has not been fully elucidated. Here, we tested the hypothesis that T 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 T and/or BMSCs. We detected a minority population of T 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 T conferred maximal neuroprotection compared to the treatment conditions containing 0%, 10%, and 100% relative ratio T. Increasing the T population resulted in increased IL6 secretion and decreased FGF-β secretion by BMSCs. This study shows that a minority population of T exists within the therapeutic BMSC population, which serves as robust mediators of the immunomodulatory and neuroprotective effect provided by BMSC transplantation.

Transient selective brain cooling confers neurovascular and functional protection from acute to chronic stages of ischemia/reperfusion brain injury

“…T cells and B cells contain subpopulations that may exert different or even opposing effects on pathological processes. [28][29][30] Further studies are warranted to test if hypothermia exerts immunosuppressive effects without decreasing the total number of lymphocytes by modifying the phenotype and function of T cell and B cell subpopulations. Alternatively, the hypothermia-induced inhibition of macrophages and neutrophils may be sufficient to reduce the expression of pro-inflammatory mediators.…”

Purinergic Profiling of Regulatory T-cells in Patients With Episodic Migraine

“…Further studies should test the contribution of other pro- and anti-inflammatory immune cells (for instance, cytokine-induced killer (CIK) T cells ( Horenstein et al, 2018 ), in migraine pathophysiology, especially in its severe and chronic forms when the inflammatory components are better presented. Several studies have investigated the neuroprotective role of Tregs in various pathological conditions such as stroke, HIV-induced encephalitis and neurodegeneration ( Liu et al, 2009 ; Gong et al, 2011 ; Li et al, 2013 ; Huang et al, 2017 ; Neal et al, 2018 ). The neuroprotective role is important in the light of recent findings showing that the brains of migrainers may exhibit microinfarctions and microlesions ( Colombo et al, 2011 ; Bashir et al, 2013 ; Hougaard et al, 2014 ).…”

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

“…attenuates inflammation more effectively than BM-MSCs alone, emphasizing BM-MSC combined therapy's potential for stroke treatment. 51 Altogether, BM-MSCs in combination with adjunctive therapies may provide enhanced functional recovery in inflammation-mediated neurodegenerative stroke models. 12,[52][53][54][55][56][57][58][59] As previously discussed, sustained and pervasive inflammation not only largely underlies secondary cell death after ischemic stroke, but also following TBI.…”