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Research Article

Gene therapy in hemiparkinsonian rhesus monkeys: long-term survival and behavioral recovery by transplantation of autologous human tyrosine hydroxylase-expressing neural stem cells

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Pages 226-237 | Received 17 Jun 2009, Accepted 13 Nov 2009, Published online: 03 Mar 2010
 

Abstract

Background aims. Neural stem cells (NSC) derived from bone marrow stromal cells (BMSC) (BMSC-D-NSC) are remarkably versatile in response to environmental signals, which render them useful in the search for neurodegenerative disease treatments. Methods. We isolated NSC from rhesus monkey bone marrow (BM), transfected them with the human tyrosine hydroxylase (hTH) gene, and transplanted them into 1-methyl-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned hemiparkinsonian rhesus monkeys to determine changes in neural transmitter production and alterations in behavior. Results. hTH-expressing cells produced monoamine agents in vitro, such as noradrenalin and dopamine. After cell transplantation in the caudate nucleus and substantia nigra of the experimental monkeys, their disease symptoms and dysfunctional glucose metabolism and dopamine transport were ameliorated. Conclusions. hTH-expressing BMSC-D-NSC survived in transplantation sites and assumed normal dopaminergic neuronal properties, playing an instrumental role in functional restoration.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 30600203) and Postdoctoral Science Foundation of China (no. 2005037124) to PhD Qiang Xu, Natural Science Foundation of China (no. U0632008, 30270491) to Prof. Ruxiang Xu, and Foundation for Key Sci-Tech Research Projects of Guangdong (no. 2008A030201019, 2007-05/06-7005206) and Guangzhou (no. 09B52120112, 2008A1-E4011-6) to Prof. Xiaodan Jiang. Non-human primate studies were supported by the Primate Animals Institute of Southern China. We also thank the staff who assisted with this study: Yuxi Zou, Mouxuan Du, Zaiyu Guo, Jianrong Chen and Junhua Rao.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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