Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair.
Olfactory ensheathing cell (OEC) transplantation has emerged as a very promising therapy for spinal cord repair. In this study, we tested the ability of genetically modified OECs to secrete high levels of glial cell line-derived neurotrophic factor (GDNF) to promote spinal cord repair. The GDNF gene was transduced into OECs using a retroviral-based system. The engineered OECs were first characterized by their ability to express and secrete biologically active GDNF in vitro. After implantation into the spinal cord of adult rats with complete spinal cord transection, OEC survival and GDNF production were examined. The locomotor functions of animals were assessed and axon regeneration was evaluated at the morphological level. To our knowledge, we report for the first time that the genetically modified OECs are capable of producing GDNF in vivo to significantly improve recovery after spinal cord injury (SCI). This work combined the outgrowth-promoting property of OECs with the neuroprotective effects of the additionally overexpressed neurotrophic factors and opens new avenues for the treatment of SCI.
Cao
Li
L
Department of Neurobiology, Second Military Medical University, Shanghai 200433, China.
Liu
Li
L
Chen
Zhe-Yu
ZY
Wang
Li-Mei
LM
Ye
Jun-Li
JL
Qiu
Hai-Yan
HY
Lu
Chang-Lin
CL
He
Cheng
C
D000818:Animals; D001369:Axons / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002469:Cell Separation / Q000379:methods; D017690:Cell Transplantation / Q000379:methods*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry / Q000379:methods; D009186:Myelin Sheath / Q000378:metabolism / Q000637:transplantation*; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D009416:Nerve Regeneration; D009830:Olfactory Bulb / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012190:Retroviridae / Q000235:genetics; D013119:Spinal Cord Injuries / Q000628:therapy*; D014161:Transduction, Genetic / Q000379:methods
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors