Zhan Jiheng, He Jianbo, Chen Meihui, Luo Dan, Lin Dingkun
Second College of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Laboratory of Osteology and Traumatology of Traditional Chinese Medicine, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Stem Cells Int. 2018 Dec 30;2018:9793845. doi: 10.1155/2018/9793845. eCollection 2018.
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 mol/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.
骨髓间充质干细胞（BMSCs）被认为是用于治疗中枢神经系统（CNS）创伤的移植细胞，但它们有限的迁移能力和归巢能力限制了其治疗效果。法舒地尔（FAS）是一种有效的Rho激酶抑制剂，据报道可减轻神经损伤并诱导BMSCs分化为神经元样细胞。然而，FAS对BMSCs迁移的影响在很大程度上仍不清楚。本研究表明，FAS在体外以30μmol/L的最佳浓度显著增强了BMSCs的迁移能力和肌动蛋白应激纤维的形成。此外，我们发现丝裂原活化蛋白激酶（MAPK）信号通路的激活参与了这些由FAS介导的现象。在体内，用FAS预处理的细胞从注射部位到脊髓损伤部位显示出更强的归巢能力。综上所述，目前的结果表明，FAS在体外和体内均作为BMSC迁移的促进因子，可能是通过MAPK信号通路诱导肌动蛋白应激纤维的形成，这表明FAS在CNS创伤的干细胞移植中可能具有协同作用。
