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Fasudil Promotes BMSC Migration via Activating the MAPK Signaling Pathway and Application in a Model of Spinal Cord Injury

机译:Fasudil通过激活MAPK信号通路和在脊髓损伤模型中促进BMSC迁移

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Bone marrow-derived mesenchymal stem cells (BMSCs) are considered as transplants for the treatment of central nervous system (CNS) trauma, but the therapeutic effect is restricted by their finite mobility and homing capacity. Fasudil (FAS), a potent Rho kinase inhibitor, has been reported to alleviate nerve damage and induce the differentiation of BMSCs into neuron-like cells. However, the effect of FAS on the migration of BMSCs remains largely unknown. The present study revealed that FAS significantly enhanced the migration ability and actin stress fiber formation of BMSCs in vitro with an optimal concentration of 30?μmol/L. Moreover, we found that activation of the MAPK signaling pathway was involved in these FAS-mediated phenomena. In vivo, cells pretreated with FAS showed greater homing capacity from the injection site to the spinal cord injury site. Taken together, the present results indicate that FAS acts as a promoting factor of BMSC migration both in vitro and in vivo, possibly by inducing actin stress fiber formation via the MAPK signaling pathway, suggesting that FAS might possess synergistic effect in stem cell transplantation of CNS trauma.
机译:骨髓衍生的间充质干细胞(BMSCs)被认为是用于治疗中枢神经系统(CNS)创伤的移植物,但治疗效果受其有限迁移率和归位能力的限制。据报道,Fasudil(Fas)是一种有效的Rho激酶抑制剂,以减轻神经损伤并诱导BMSC的分化为神经元样细胞。然而,Fas对BMSC的迁移的影响仍然很大程度上是未知的。本研究表明,Fas显着提高了迁移能力,并在体外具有30μmol/升的最佳浓度。此外,我们发现MAPK信号通路的激活涉及这些FAS介导的现象。在体内,用Fas预处理的细胞显示出从注射部位到脊髓损伤部位的更大归巢量。本结果表明,FAS作为BMSC迁移的促进因子在体外和体内,可能是通过MAPK信号传导途径诱导肌动蛋白应激纤维形成,表明FAS可能具有CNS干细胞移植中的协同作用创伤。

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