Sciatic Nerve Regeneration by Microporous Nerve Conduits Seeded With Glial Cell Line-Derived Neurotrophic Factor or Brain-Derived Neurotrophic Factor Gene Transfected Neural Stem Cells
Article first published online: 14 FEB 2011
© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
Volume 35, Issue 4, pages 363–372, April 2011
How to Cite
Fu, K.-Y., Dai, L.-G., Chiu, I.-M., Chen, J.-R. and Hsu, S.-h. (2011), Sciatic Nerve Regeneration by Microporous Nerve Conduits Seeded With Glial Cell Line-Derived Neurotrophic Factor or Brain-Derived Neurotrophic Factor Gene Transfected Neural Stem Cells. Artificial Organs, 35: 363–372. doi: 10.1111/j.1525-1594.2010.01105.x
- Issue published online: 19 APR 2011
- Article first published online: 14 FEB 2011
- Received October 2009; revised June 2010.
- Glial cell line-derived neurotrophic factor;
- Brain-derived neurotrophic factor;
- Neural stem cells;
- Nerve regeneration
Neurotrophic factors such as the glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) promote nerve cell survival and regeneration, but their efficacy in repairing a longer gap defect of rat sciatic nerve (15 mm) has not been established. In this study, two recombinant mammalian vectors containing either rat GDNF gene or BDNF gene were constructed and each was transfected into neural stem cells (NSCs). It was found that the transfection of GDNF or BDNF gene into NSCs led to significantly enhanced expression of GDNF or BDNF mRNA. The amount of GDNF or BDNF protein secreted from the transfected NSCs showed a 3.3-fold or 2.5-fold increase than that from nontransfected NSCs, respectively. The regeneration capacity of rat sciatic nerve in a poly(D,L-lactide) conduit seeded with GDNF or BDNF-transfected NSCs was evaluated by the histology, functional gait, and electrophysiology after 8 weeks of implantation. It was observed that the degree of myelination and the size of regenerated tissue in the conduits seeded with GDNF- and BDNF-transfected NSCs were higher than those seeded with the nontransfected NSCs. Conduits seeded with GDNF-transfected NSCs had the greatest number of blood vessels. The functional recovery assessed by the functional gait and electrophysiology was significantly improved for conduits seeded with GDNF or BDNF-transfected NSCs. It was concluded that the genetically modified NSCs may have potential applications in promoting nerve regeneration and functional recovery.