The role of hepatocyte growth factor in mesenchymal stem cell-induced recovery in spinal cord injured rats

Stem Cell Research & Therapy

Tianyu Han¹  Xia Xiang¹  Cailiang Shen¹  Peiwen Song¹  Yang Niu¹  Ying Wang²  Huang Fang³ 

[1] Department of Orthopedics (Spinal Surgery), The First Affiliated Hospital of Anhui Medical University;Department of Radiology, The First Affiliated Hospital of Anhui Medical University;Department of Spinal Surgery, The First Affiliated Hospital of USTC;

关键词: Neural stem cells;    Mesenchymal stem cells;    Bone morphogenetic proteins;    Hepatocyte growth factor;    Inflammation;   

DOI  :  10.1186/s13287-020-01691-x

来源: DOAJ

【 摘 要 】

Abstract Background Mesenchymal stem cells (MSCs) have become a promising treatment for spinal cord injury (SCI) due to the fact that they provide a favorable environment. Treatment using MSCs results in a better neurological functional improvement through the promotion of nerve cell regeneration and the modulation of inflammation. Many studies have highlighted that the beneficial effects of MSCs are more likely associated with their secreted factors. However, the identity of the factor that plays a key role in the MSC-induced neurological functional recovery following SCI as well as its molecular mechanism still remains unclear. Methods A conditioned medium (collected from the MSCs) and hepatocyte growth factor (HGF) were used to test the effects on the differentiation of neural stem cells (NSCS) in the presence of BMP4 with or without a c-Met antibody. In SCI rats, Western blot, ELISA, immunohistochemistry, and hematoxylin-eosin staining were used to investigate the biological effects of MSC-conditioned medium and HGF on nerve cell regeneration and inflammation with or without the pre-treatment using a c-Met antibody. In addition, the possible molecular mechanism (cross-talk between HGF/c-Met and the BMP/Smad 1/5/8 signaling pathway) was also detected by Western blot both in vivo and in vitro. Results The conditioned medium from bone marrow-derived MSCs (BMSCs) was able to promote the NSC differentiation into neurons in vitro and the neurite outgrowth in the scar boundary of SCI rats by inhibiting the BMP/Smad signaling pathway as well as reduces the secondary damage through the modulation of the inflammatory process. The supplementation of HGF showed similar biological effects to those of BMSC-CM, whereas a functional blocking of the c-Met antibody or HGF knockdown in BMSCs significantly reversed the functional improvement mediated by the BMSC-CM. Conclusions The MSC-associated biological effects on the recovery of SCI rats mainly depend on the secretion of HGF.

【 授权许可】

Unknown