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Muse cells decrease the neuroinflammatory response by modulating the proportion of M1 and M2 microglia in vitro

Neural Regeneration Research 2023年第1期18卷 213-218页

作者： Xin-Yao Yin Chen-Chun Wang Pan Du Xue-Song Wang Yi-Chi Lu Yun-Wei Sun Yue-Hui Sun Yi-Man Hu Xue Chen Department of Basic Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu ProvinceChina Department of Orthopedics Affiliated Hospital of Jiangnan UniversityWuxiJiangsu ProvinceChina

Neuroinflammation hinders repair of the central nervous system(CNS).Stem cell transplantation is a very promising approach for treatment of CNS injuries.However,it is difficult to select seed cells that can both facilitate nerve regeneration and improve the microenvironment in the CNS.In this study,we isolated multilineage-differentiating stress-enduring(Muse)cells from bone marrow mesenchymal stem cells.We explored the anti-inflammatory effect and mechanism of Muse cells in vitro by coculture of Muse cells with lipopolysaccharide-stimulated microglia.Our results showed that Muse cells effectively reduced the transcription and secretion of tumor necrosis factorαand interleukin-1βand increased the expression of transforming growth factor-βand interleukin-10 in microglia.In addition,Muse cells decreased the number of M1 microglia and increased the proportion of M2 microglia in an inflammatory environment more effectively than bone marrow mesenchymal stem cells.We also show that Muse cells inhibited the protein expression of toll-like receptor 4(TLR4)and myeloid differentiation primary response protein(MyD88)and inhibited the expression of the phosphorylated forms of transcription factor p65,nuclear factor(NF)-κB inhibitor alpha,and p38 mitogen-activated protein kinase(MAPK)in microglia.Therefore,we suggest Muse cells cause antineuroinflammatory effects by inhibition of the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways in microglia.Our results shed light on the function of Muse cells in relation to CNS diseases and provide insight into the selection of seed cells.

关键词： bone marrow mesenchymal stem cells central nervous system lipopolysaccharide multilineage-differentiating stress-enduring cells neuroinflammation microglia signaling pathway

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