Co-transplantation of GDNF-overexpressing neural stem cells and fetal dopaminergic neurons mitigates motor symptoms in a rat model of Parkinson's disease.

Abstract

Striatal transplantation of dopaminergic (DA) neurons or neural stem cells (NSCs) has been reported to improve the symptoms of Parkinson's disease (PD), but the low rate of cell survival, differentiation, and integration in the host brain limits the therapeutic efficacy. We investigated the therapeutic effects of intracranial co-transplantation of mesencephalic NSCs stably overexpressing human glial-derived neurotrophic factor (GDNF-mNSCs) together with fetal DA neurons in the 6-OHDA rat model of PD. Striatal injection of mNSCs labeled by the contrast enhancer superparamagnetic iron oxide (SPIO) resulted in a hypointense signal in the striatum on T2-weighted magnetic resonance images that lasted for at least 8 weeks post-injection, confirming the long-term survival of injected stem cells in vivo. Co-transplantation of GDNF-mNSCs with fetal DA neurons significantly reduced apomorphine-induced rotation, a behavioral endophenotype of PD, compared to sham-treated controls, rats injected with mNSCs expressing empty vector (control mNSCs) plus fetal DA neurons, or rats injected separately with either control mNSCs, GDNF-mNSCs, or fetal DA neurons. In addition, survival and differentiation of mNSCs into DA neurons was significantly greater following co-transplantation of GDNF-mNSCs plus fetal DA neurons compared to the other treatment groups as indicated by the greater number of cell expressing both the mNSCs lineage tracer enhanced green fluorescent protein (eGFP) and the DA neuron marker tyrosine hydroxylase. The success of cell-based therapies for PD may be greatly improved by co-transplantation of fetal DA neurons with mNSCs genetically modified to overexpress trophic factors such as GDNF that support differentiation into DA cells and their survival in vivo.

• Authors: Xingli Deng, Yuanxin Liang, Hua Lu, Zhiyong Yang, Ru'en Liu, Jinkun Wang, Xiaobin Song, Jiang Long, Yu Li, Deqiang Lei, Zhongtang Feng
• Journal: PloS one (PLoS One) Vol. 8 Issue 12 Pg. e80880 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24312503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gdnf protein, rat
• Glial Cell Line-Derived Neurotrophic Factor

Topics

• Allografts
• Animals
• Cell Differentiation (genetics)
• Cell Line, Tumor
• Cell Survival
• Disease Models, Animal
• Dopaminergic Neurons (metabolism, transplantation)
• Fetus
• Glial Cell Line-Derived Neurotrophic Factor (genetics, metabolism)
• Humans
• Motor Activity
• Neural Stem Cells (metabolism, transplantation)
• Parkinson Disease (genetics, metabolism, pathology, physiopathology, therapy)
• Rats
• Rats, Sprague-Dawley
• Stem Cell Transplantation