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Brain Advance Access originally published online on December 22, 2003
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Brain, Vol. 127, No. 3, 535-549, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh072

Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair

Li Cao1, Li Liu1,2, Zhe-Yu Chen1, Li-Mei Wang1, Jun-Li Ye1,2, Hai-Yan Qiu1,2, Chang-Lin Lu1 and Cheng He1

1 Department of Neurobiology, Second Military Medical University, Shanghai 200433 and 2 Department of Pathophysiology, Qingdao Medical College of Qingdao University, Shandong 266021, China.

Correspondence to: Cheng He, Department of Neurobiology, Second Military Medical University, Shanghai 200433, China E-mail: chenghe{at}online.sh.cn

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.

Key Words: spinal cord injury; olfactory ensheathing cell; glial cell line-derived neurotrophic factor; transplantation; gene therapy

Abbreviations: CM = conditioned medium; CSN = corticospinal neuron; CST = corticospinal tract; DMEM = Dulbecco’s modified Eagle medium; GDNF = glial cell line-derived neurotrophic factor; GDNF = glial cell line-derived neurotrophic factor; GFAP = glial fibrillary acidic protein; GFP = green fluorescent protein; HRP = horseradish peroxidase; LTR = long terminal repeat; NF = neurofilament; OECs = olfactory ensheathing cells; PBS = phosphate-buffered saline; RSN = rubrospinal neuron; SCI = spinal cord injury

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Received August 4, 2003. Revised October 23, 2003. Accepted October 24, 2003.

Li Cao and Li Liu contributed equally to the study


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