title: Autologous mesenchymal stem cell-derived dopaminergic neurons function in parkinsonian macaques.
abstract: A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson's disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [11C]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson's disease.
authors.affiliation: Functional Probe Research Laboratory, Center for Molecular Imaging Science, RIKEN, Kobe, Japan. takuya.hayashi@riken.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shohei
authors.initials: S
authors.lastname: Wakao
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kitada
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ose
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watabe
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Kanae
authors.initials: K
authors.lastname: Mitsunaga
authors.forename: Dai
authors.initials: D
authors.lastname: Matsuse
authors.forename: Taeko
authors.initials: T
authors.lastname: Shigemoto
authors.forename: Akihito
authors.initials: A
authors.lastname: Ito
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ikeda
authors.forename: Hidenao
authors.initials: H
authors.lastname: Fukuyama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Onoe
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Mari
authors.initials: M
authors.lastname: Dezawa
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D005786:Gene Expression Regulation; D039161:Integrin alpha6beta4 / Q000096:biosynthesis; D008252:Macaca fascicularis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy*; D049268:Positron-Emission Tomography; D011859:Radiography; D014182:Transplantation, Autologous
chemical_list: D000943:Antigens, Differentiation; D039161:Integrin alpha6beta4