Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, China.
Department of Neurology, The Third People's Hospital of Yancheng (Yancheng Clinical Institute, Nanjing Medical University), 75 Juchang Road, Yancheng, 224000, Jiangsu, China.
Neuromolecular Med. 2022 Sep;24(3):290-298. doi: 10.1007/s12017-021-08686-8. Epub 2022 Jan 10.
Mesenchymal stem cells-derived exosome (MSCs-exo) is a potential method for cerebral infarction (CI) treatment. Here, western blot and qRT-PCR were carried out to measure the expression of proteins and genes, respectively. Modified neurological severity score and TTC staining were used to evaluate the brain injury of middle cerebral artery occlusion (MCAO) rats. Immunohistochemistry was performed to detect the expression of Iba-1, iNOS, and Arg-1 in tissues. Moreover, the rate of M1/M2 microglia was ensured by flow cytometry, and the concentration of pro-inflammatory factors in medium was measured using ELISA. Here, we found that miR-23a-3p is increased in human umbilical cord blood MSCs-exo. Bone marrow MSCs-exo (BMSCs-exo) could improve the injury in neuronal function and reduce the infarct size in vivo. However, the improvement of BMSCs-exo to CI was reversed by miR-23a-3p knockdown. The inhibition of BMSCs-exo to MCAO-induced microglia activation and M1 polarization and the upregulation of pro-inflammatory factors were limited by miR-23a-3p knockdown, which also confirmed in lipopolysaccharide-induced microglia. Overall, our data indicated that MSCs-exo improves CI via transferring miR-23a-3p, thus to induce the deactivation of microglia and M2 polarization. Our study revealed a new regulatory mechanism of CI.
间充质干细胞来源的外泌体 (MSCs-exo) 是治疗脑梗死 (CI) 的一种有潜力的方法。在这里，我们通过 Western blot 和 qRT-PCR 分别测量了蛋白质和基因的表达。改良神经功能缺损评分和 TTC 染色用于评估大脑中动脉闭塞 (MCAO) 大鼠的脑损伤。免疫组织化学用于检测组织中 Iba-1、iNOS 和 Arg-1 的表达。此外，通过流式细胞术确定 M1/M2 小胶质细胞的比例，并使用 ELISA 测量培养基中促炎因子的浓度。在这里，我们发现 miR-23a-3p 在人脐带来源的间充质干细胞来源的外泌体中增加。骨髓间充质干细胞来源的外泌体 (BMSCs-exo) 可以改善神经元功能损伤并减少体内梗死面积。然而，miR-23a-3p 敲低逆转了 BMSCs-exo 对 CI 的改善。BMSCs-exo 对 MCAO 诱导的小胶质细胞激活和 M1 极化的抑制以及促炎因子的上调受到 miR-23a-3p 敲低的限制，这在脂多糖诱导的小胶质细胞中也得到了证实。总体而言，我们的数据表明 MSCs-exo 通过转移 miR-23a-3p 来改善 CI，从而诱导小胶质细胞失活和 M2 极化。我们的研究揭示了 CI 的一种新的调控机制。
