title: Transplantation of mouse CGR8 embryonic stem cells producing GDNF and TH protects against 6-hydroxydopamine neurotoxicity in the rat.
abstract: Embryonic stem cells (ESCs)-based therapies have been increasingly recognized as a potential tool to replace or support cells and their function damaged by the neurodegenerative process that underlies Parkinson's disease (PD). In this study, we implanted engineered mouse embryonic stem (ES) CGR8 cells, which stably co-express glial cell line-derived neurotrophic factor (GDNF) and tyrosine hydroxylase (TH), into striatum (Str) or both Str and substantia nigra (SN) of parkinsonian rats lesioned by 6-hydroxydopamine (6-OHDA). We found that cell transplantation into Str or both Str and SN rescued behavioral abnormalities and striatal DA depletion associated with 6-OHDA lesion. Our findings suggested that the profound functional impairment in nigrostriatal circuitry could be at least partially restored by ESCs-based expression of TH and GDNF, which may be developed into a useful tool for PD therapy.
authors.affiliation: Research Institute for Cerebrovascular Disease, Qingdao 266071, China.
authors.forename: Tian-wei
authors.initials: TW
authors.lastname: Liu
authors.forename: Ze-gang
authors.initials: ZG
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jun-xia
authors.initials: JX
authors.lastname: Xie
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005260:Female; D015316:Genetic Therapy; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018696:Neuroprotective Agents / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000628:therapy; D016627:Oxidopamine / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase