Brain-2004-Cao-535-49.pdfVIP

Olfactory ensheathing cells genetically modi?ed to secrete GDNF to promote spinal cord repair Li Cao,1 Li Liu,1,2 Zhe-Yu Chen,1 Li-Mei Wang,1 Jun-Li Ye,1,2 Hai-Yan Qiu,1,2 Chang-Lin Lu1 and and Cheng He1 1Department of Neurobiology, Second Military Medical University, Shanghai 200433 and 2Department of Pathophysiology, Qingdao Medical College of Qingdao University, Shandong 266021, China. Li Cao and Li Liu contributed equally to the study Correspondence to: Cheng He, Department of Neurobiology, Second Military Medical University, Shanghai 200433, China E-mail: chenghe@ Summary 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 modi?ed 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 ?rst 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 regener- ation was evaluated at the morphological level. To our knowledge, we report for the ?rst time that the genetic- ally modi?ed OECs are capable of producing GDNF in vivo to signi?cantly 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. Keywords: 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 = Dulbeccos modi?ed Eagle medium; GDNF = glial cell line-derived ne