title: Genetically modified Schwann cells producing glial cell line-derived neurotrophic factor inhibit neuronal apoptosis in rat spinal cord injury.
abstract: Schwann cells (SCs) are the major cells constituting the peripheral nerve structure and function, and also secret a variety of neurotrophic factors. Schwann cell (SC) transplantation has recently emerged as a promising therapeutic strategy for spinal cord injury (SCI). In the present study, the ability of genetically modified SCs producing high levels of glial cell line‑derived neurotrophic factor (GDNF) to promote spinal cord repair was assessed. The GDNF gene was transduced into SCs. The engineered SCs were characterized by their ability to express and secrete biologically active GDNF, which was shown to inhibit apoptosis of primary rat neurons induced by radiation, and upregulate the expression of B‑cell lymphoma 2 (Bcl‑2) and downregulate the expression of Bcl‑2 associated X protein (Bax) in vitro. Following SC implantation into the spinal cord of adult rats with SCI induced by weight‑drop impact, the survival of rats with transplanted SCs, histology of the spinal cord and expression levels of Bcl‑2 and Bax were examined. Transplantation of unmodified and genetically modified SCs producing GDNF attenuated SCI by inhibiting apoptosis via the Bcl‑2/Bax pathways. The genetically modified SCs demonstrated markedly improved recovery of SCI as compared with unmodified SCs. The present study combined the outgrowth‑promoting property of SCs with the neuroprotective effects of overexpressed GDNF and identified this as a potential novel therapeutic strategy for SCI.
authors.affiliation: Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Guomin
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Xukai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Guoxi
authors.initials: G
authors.lastname: Shao
authors.affiliation: Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Qinyi
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D018920:Coculture Techniques; D005260:Female; D015316:Genetic Therapy; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000627:therapeutic use*; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000378:metabolism / Q000637:transplantation*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D051028:bcl-2-Associated X Protein