Hepatocyte growth factor modified human umbilical cord mesenchymal stem cell therapy promotes remyelination after intracerebral hemorrhage in rats

AIM: To study the effects of neurological improvement and remyelination after intracranial hemorrhage (ICH) in rats by a novel therapeutic strategy with hepatocyte growth factor (HGF) gene transfected human umbilical cord mesenchymal stem cells (hUCMSCs) by lentiviral vector. METHODS: ICH was induced in 60 adult male Sprague-Dawley rats by a stereotactically guided injection of bacterial type IV collagenase into the right internal capsule. Non-modified hUCMSCs, HGF-modified hUCMSCs with lentiviral vector or PBS were administered left intraventricularly 7 d after right internal capsule ICH. All rats underwent modified neurological severity scores for 35 d. Luxol fast blue staining, immunohistological staining and Western blotting assessments for myelin basic protein (MBP) were applied. RESULTS: The ICH rats receiving HGF-modified hUCMSCs demonstrated significant functional recovery, determined by modified neurological severity scores, compared to the other groups from 2 weeks after cell therapy. As indicated by Luxol fast blue staining, the percent area of demyelination was obviously reduced in the HGF-hUCMSC treatment group compared to the PBS control group and hUCMSC-only treatment group at 5 weeks after ICH. The expression of MBP detected by immunohistological staining and Western blotting was significantly higher in HGF-hUCMSCs treated brain than that in other groups (P<0.01). CONCLUSION: Our data suggest that the HGF gene-modified hUCMSCs contribute to the remarkable functional recovery after ICH compared to hUCMSCs transplantation alone. The treatment promotes nerve fiber remyelination by up-regulating the MBP after ICH in rats.