Yin Xin-Yao, Wang Chen-Chun, Du Pan, Wang Xue-Song, Lu Yi-Chi, Sun Yun-Wei, Sun Yue-Hui, Hu Yi-Man, Chen Xue
Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, China.
Department of Orthopedics, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China.
Neural Regen Res. 2023 Jan;18(1):213-218. doi: 10.4103/1673-5374.343885.
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 factor α and interleukin-1β and increased the expression of transforming growth factor-β and 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.
神经炎症阻碍中枢神经系统（CNS）的修复。干细胞移植是治疗中枢神经系统损伤非常有前景的方法。然而，很难选择既能促进神经再生又能改善中枢神经系统微环境的种子细胞。在本研究中，我们从骨髓间充质干细胞中分离出多能分化应激耐受（Muse）细胞。我们通过将Muse细胞与脂多糖刺激的小胶质细胞共培养，在体外探索了Muse细胞的抗炎作用及机制。我们的结果表明，Muse细胞有效降低了肿瘤坏死因子α和白细胞介素-1β的转录和分泌，并增加了小胶质细胞中转化生长因子-β和白细胞介素-10的表达。此外，在炎症环境中，Muse细胞比骨髓间充质干细胞更有效地减少了M1小胶质细胞的数量并增加了M2小胶质细胞的比例。我们还表明，Muse细胞抑制了Toll样受体4（TLR4）和髓样分化初级反应蛋白（MyD88）的蛋白表达，并抑制了小胶质细胞中转录因子p65、核因子（NF）-κB抑制因子α和p38丝裂原活化蛋白激酶（MAPK）磷酸化形式的表达。因此，我们认为Muse细胞通过抑制小胶质细胞中的TLR4/MyD88/NF-κB和p38 MAPK信号通路产生抗神经炎症作用。我们的结果揭示了Muse细胞在中枢神经系统疾病中的功能，并为种子细胞的选择提供了见解。
