title: Heat shock protein 60 affects behavioral improvement in a rat model of Parkinson's disease grafted with human umbilical cord mesenchymal stem cell-derived dopaminergic-like neurons.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder that is caused by a loss of dopaminergic (DAergic) neurons in mesencephalic substantia nigra (SN). Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of self-renewal and differentiation into multiple cell lineages, including DAergic neurons. Thus, hUC-MSCs could be a promising alternative to compensate for the loss of DAergic neurons in PD. In the current study, hUC-MSCs and hUC-MSCs-derived DAergic-like neurons were transplanted into the striatum and SN of a rat model of PD that is induced by 6-hydroxydopamine (6-OHDA). We evaluated their therapeutic effects on improving rotation behavior in the rat and on modulating the level of heat shock protein 60 (Hsp60) expression in the brain. After transplantation, an amelioration of rotation behavior was observed in rats that underwent cell grafting, and hUC-MSCs-derived DAergic-like neurons were superior to hUC-MSCs at inducing behavioral improvement. Western blot and immunohistochemistry analysis indicated significantly elevated levels of Hsp60 in cell-grafted rats compared to 6-OHDA-lesioned (PD) rats. These results demonstrate that hUC-MSCs-based cell transplantation is potential therapeutic treatment for PD, and hUC-MSCs-derived DAergic-like neurons appear to be favorable candidates for cell replacement therapy in PD. Finally, Hsp60 could be involved in a mechanism of behavioral recovery.
authors.affiliation: Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Xian-Jing
authors.initials: XJ
authors.lastname: Zhao
authors.affiliation: Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Zheng-Xia
authors.initials: ZX
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China. mjfeng416@aliyun.com.
authors.forename: Mei-Jiang
authors.initials: MJ
authors.lastname: Feng
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000096:biosynthesis*; D003342:Corpus Striatum / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000637:transplantation*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014470:Umbilical Cord / Q000166:cytology / Q000637:transplantation*
chemical_list: D018834:Chaperonin 60; C557067:Hspd1 protein, rat; D024101:Mitochondrial Proteins
keywords: Cell replacement therapy; Dopaminergic-like neuron; Heat shock protein 60; Human umbilical cord mesenchymal stem cell; Parkinson’s disease