PMC:6141714 / 126497-128901 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6141714","sourcedb":"PMC","sourceid":"6141714","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6141714","text":"Together, these results indicate that the improvement in the clinical condition observed after the administration of hMSCs is a consequence of the inhibition in the proliferation and infiltration of inflammatory cells such as B, Th1 and Th17 lymphocytes, neutrophils and monocytes into the central nervous system and spinal cord promoted by these stem cells. It can be hypothesized that factors secreted by the hMSCs administered such as IL-10, IL-4, TGF-β, PGE2, HGF, and PDL-1 acts by inhibiting the activation of autoreactive CD4+ T cells and their differentiation in Th1 cells in both the periphery and central nervous system and by stimulating the differentiation of these CD4+ T cells into Th2 and Treg lymphocytes. Additionally, these factors can stimulate APCs located in both the periphery and central nervous system to differentiate into regulatory dendritic cells, further inhibiting the activation of autoreactive CD4+ T cells. The recruitment of pro-inflammatory cells such as neutrophils, basophils, monocytes, eosinophils and CD8+T lymphocytes and their infiltration into the central nervous system can also be inhibited as a result of the decrease in the secretion of pro-inflammatory cytokines and growth factors such as IFN-γ, IL-2, and TGF-β by Th1 lymphocytes and due to the secretion of anti-inflammatory factors such as GM-CSF, PGE2, and IL-6 by the hMSCs administered. The decrease in the levels of pro-inflammatory cytokines and growth factors and the secretion of anti-inflammatory factors by hMSCs can also inhibit the activation of astrocytes in the central nervous system and stimulate pro-inflammatory cells to differentiate into M2 macrophages and cells with immunomodulatory properties such and Breg cells. As a result, the secretion of TNF-α, proteases, nitric oxide and myelin-specific antibodies by pro-inflammatory cells located in the central nervous system is also inhibited, decreasing the death of oligodendrocytes and the destruction of the myelin sheath in axons. Finally, the secretion of neurotrophic factors such as BDNF, CNTF, GDNF, NGF, and NTF3 by the hMSCs administered may also act on oligodendrocytes and neurons, further inhibiting the progression of the disease. The mechanism proposed by this systematic review concerning the inhibition in the progression of the pathological process of multiple sclerosis mediated by hMSCs is represented in Figure 7.","tracks":[]}