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  • "glia cell line–derived neurotrophic factor" x
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Fu-Chou Cheng, Ming-Hong Tai, Meei-Ling Sheu, Chun-Jung Chen, Dar-Yu Yang, Hong-Lin Su, Shu-Peng Ho, Shu-Zhen Lai and Hung-Chuan Pan

Object

Human amniotic fluid–derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration, and the local delivery of neurotrophic factors may additionally enhance nerve regeneration capacity. The present study evaluates whether the transplantation of glia cell line–derived neurotrophic factor (GDNF)–modified human AFMSCs may enhance regeneration of sciatic nerve after a crush injury.

Methods

Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. Either GDNF-modified human AFMSCs or human AFMSCs were embedded in Matrigel and delivered to the injured nerve. Motor function and electrophysiological studies were conducted after 1 and 4 weeks. Early or later nerve regeneration markers were used to evaluate nerve regeneration. The expression of GDNF in the transplanted human AFMSCs and GDNF-modified human AFMSCs was monitored at 7-day intervals.

Results

Human AFMSCs were successfully transfected with adenovirus, and a significant amount of GDNF was detected in human AFMSCs or the culture medium supernatant. Increases in the sciatic nerve function index, the compound muscle action potential ratio, conduction latency, and muscle weight were found in the groups treated with human AFMSCs or GDNF-modified human AFMSCs. Importantly, the GDNF-modified human AFMSCs induced the greatest improvement. Expression of markers of early nerve regeneration, such as increased expression of neurofilament and BrdU and reduced Schwann cell apoptosis, as well as late regeneration markers, consisting of reduced vacuole counts, increased expression of Luxol fast blue and S100 protein, paralleled the results of motor function. The expression of GDNF in GDNF-modified human AFMSCs was demonstrated up to 4 weeks; however, the expression decreased over time.

Conclusions

The GDNF-modified human AFMSCs appeared to promote nerve regeneration. The consecutive expression of GDNF was demonstrated in GDNF-modified human AFMSCs up to 4 weeks. These findings support a nerve regeneration scenario involving cell transplantation with additional neurotrophic factor secretion.

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Dar-Yu Yang, Meei-Ling Sheu, Hong-Lin Su, Fu-Chou Cheng, Ying-Ju Chen, Chun-Jung Chen, Wen-Ta Chiu, Jia-Jean Yiin, Jason Sheehan and Hung-Chuan Pan

Veterans General Hospital for their assistance with the statistical analysis. This article contains some figures that are displayed in color online but in black-and-white in the print edition. References 1 Bain JR , Mackinnon SE , Hunter DA : Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat . Plast Reconstr Surg 83 : 129 – 138 , 1989 2 Cheng FC , Tai MH , Sheu ML , Chen CJ , Yang DY , Su HL , : Enhancement of regeneration with glia cell line-derived neurotrophic factor

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Meei-Ling Sheu, Fu-Chou Cheng, Hong-Lin Su, Ying-Ju Chen, Chun-Jung Chen, Chih-Ming Chiang, Wen-Ta Chiu, Jason Sheehan and Hung-Chuan Pan

WY , Chen SY , Wu CW , : Transplantation of bone marrow stromal cells for peripheral nerve repair . Exp Neurol 204 : 443 – 453 , 2007 4 Chen ZY , Chai YF , Cao L , Lu CL , He C : Glial cell line-derived neurotrophic factor enhances axonal regeneration following sciatic nerve transection in adult rats . Brain Res 902 : 272 – 276 , 2001 5 Cheng FH , Tai MH , Sheu ML , Chen CJ , Yang DY , Su HL , : Enhancement of regeneration with glia cell line–derived neurotrophic factor–transduced human amniotic fluid