title: Up-regulation of stromal cell-derived factor-1 enhances migration of transplanted neural stem cells to injury region following degeneration of spiral ganglion neurons in the adult rat inner ear.
abstract: Neural stem cell (NSC) transplantation into the cochlea is widely used for the treatment of spiral ganglion neuron (SGN) degenerative disease and injury in the animal models, but the migration of the transplanted NSCs to the injury region is difficult and the mechanism is still unclear. In this study, we aimed to validate whether the SGN-degenerated cochlear microenvironment plays a role in the NSC migration and investigated whether stromal cell-derived factor-1 (SDF-1) was involved in the NSCs migration. Using a rat SGN degeneration model, we demonstrated that the transplanted NSCs are more likely to migrate to the injury region during the early post-injury (EPI) than the late post-injury (LPI) stage and the control cochlea. We found that the expressions of SDF-1 increased transiently after SGN degeneration. Additionally, we showed that the NSCs express CXCR4, a receptor for SDF-1. We observed that the region to which the transplanted NSC localized coincides with the region where the SDF-1 is highly expressed following the degeneration of SGNs. Finally, we observed that the increased SDF-1 is derived from the Schwann cells in the SGN-degenerated model. These results suggest that SDF-1, which is derived from cochlear Schwann cells and up-regulated in the early injury microenvironment, plays a beneficial role in the NSC migration to the injury region. Optimizing SDF-1 expression in the host microenvironment or increasing the CXCR4 expression of the donor stem cells may improve the migration efficiency of transplanted cells toward the injury region in the cochlea.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Peng-Zhi
authors.initials: PZ
authors.lastname: Zhang
authors.forename: Ya
authors.initials: Y
authors.lastname: He
authors.forename: Xing-Wang
authors.initials: XW
authors.lastname: Jiang
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Xue
authors.forename: Ke
authors.initials: K
authors.lastname: Zhou
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Wu
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Mi
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Qiu
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D009474:Neurons / Q000473:pathology*; D009830:Olfactory Bulb / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D013136:Spiral Ganglion / Q000293:injuries / Q000378:metabolism / Q000473:pathology*
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4