title: Transplanted hUCB-MSCs migrated to the damaged area by SDF-1/CXCR4 signaling to promote functional recovery after traumatic brain injury in rats.
abstract: Transplanted human umbilical cord mesenchymal stem cells (hUC-MSCs) have exhibited considerable therapeutic potential for traumatic brain injury (TBI). However, how hUC-MSCs migrating to the injury region and the mechanism of hUC-MSCs promoting functional recovery after TBI are still unclear. In this study, we investigated whether stromal cell-derived factor-1 (SDF-1) was involved in the hUC-MSCs migration and the possible mechanisms that might be involved in the beneficial effect on functional recovery. In vitro experiments demonstrated that SDF-1 induces a concentration-dependent migration of hUC-MSCs. Furthermore, pre-treatment with the CXCR4-specific antagonist AMD3100 significantly prevented the migration of hUC-MSCs in vitro. We found that the expression of SDF-1 increased significantly around the damaged area. Transplanted hUC-MSCs were localized to regions where SDF-1 was highly expressed. Additionally, our results showed that hUC-MSCs-treated animals showed significantly improved functional recovery compared with controls. In hUC-MSCs-transplanted group, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were decreased and BrdU-positive cells were significantly increased compared with control group, more of BrdU-positive cells co-localized with GFAP. These suggest that SDF-1 plays an important role in the migration of hUC-MSCs to the damaged area and hUC-MSCs are beneficial for functional recovery after TBI.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ma
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Yi
authors.forename: Xiaochong
authors.initials: X
authors.lastname: Zhang
authors.forename: Bing Bing
authors.initials: BB
authors.lastname: Gao
authors.forename: Yesen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ruxiang
authors.initials: R
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D012333:RNA, Messenger; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D019718:Receptors, CXCR4
keywords: SDF-1/CXCR4; Traumatic brain injury,; hUCB-MSCs,