Skip Navigation


Brain Advance Access originally published online on December 22, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary figures in colour
Right arrow All Versions of this Article:
127/3/535    most recent
awh072v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (38)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Cao, L.
Right arrow Articles by He, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cao, L.
Right arrow Articles by He, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

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

.

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

Li Cao and Li Liu contributed equally to the study


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
Z. Su, L. Cao, Y. Zhu, X. Liu, Z. Huang, A. Huang, and C. He
Nogo enhances the adhesion of olfactory ensheathing cells and inhibits their migration
J. Cell Sci., June 1, 2007; 120(11): 1877 - 1887.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. Lu, H. Yang, M. Culbertson, L. Graham, A. J. Roskams, and M. H. Tuszynski
Olfactory Ensheathing Cells Do Not Exhibit Unique Migratory or Axonal Growth-Promoting Properties after Spinal Cord Injury
J. Neurosci., October 25, 2006; 26(43): 11120 - 11130.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
Y. Zhang, W. Zhu, Y.-G. Wang, X.-J. Liu, L. Jiao, X. Liu, Z.-H. Zhang, C.-L. Lu, and C. He
Interaction of SH2-B{beta} with RET is involved in signaling of GDNF-induced neurite outgrowth
J. Cell Sci., April 15, 2006; 119(8): 1666 - 1676.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. Girard, A.-P. Bemelmans, N. Dufour, J. Mallet, C. Bachelin, B. Nait-Oumesmar, A. Baron-Van Evercooren, and F. Lachapelle
Grafts of Brain-Derived Neurotrophic Factor and Neurotrophin 3-Transduced Primate Schwann Cells Lead to Functional Recovery of the Demyelinated Mouse Spinal Cord
J. Neurosci., August 31, 2005; 25(35): 7924 - 7933.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
M. J. Ruitenberg, D. B. Levison, S. V. Lee, J. Verhaagen, A. R. Harvey, and G. W. Plant
NT-3 expression from engineered olfactory ensheathing glia promotes spinal sparing and regeneration
Brain, April 1, 2005; 128(4): 839 - 853.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.