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Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques
Takuya Hayashi, … , Yasuhiko Tabata, Mari Dezawa
Takuya Hayashi, … , Yasuhiko Tabata, Mari Dezawa
Published December 3, 2012
Citation Information: J Clin Invest. 2013;123(1):272-284. https://doi.org/10.1172/JCI62516.
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Research Article Neuroscience Article has an altmetric score of 32

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

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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

Takuya Hayashi, Shohei Wakao, Masaaki Kitada, Takayuki Ose, Hiroshi Watabe, Yasumasa Kuroda, Kanae Mitsunaga, Dai Matsuse, Taeko Shigemoto, Akihito Ito, Hironobu Ikeda, Hidenao Fukuyama, Hirotaka Onoe, Yasuhiko Tabata, Mari Dezawa

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Figure 4

Evaluation of tumorigenicity of MSC-DP–grafted animals.

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Evaluation of tumorigenicity of MSC-DP–grafted animals.
(A) SUV images o...
(A) SUV images of 18F-FDG PET scans, obtained 8 months after engraftment, are shown for each animal in the engrafted group. No apparently high uptake of 18F-FDG was found in any of MSC-DP cell–engrafted animals. (B) Immunostaining with Ki-67 is shown in a section of MSC-DP cell–engrafted striatum. Cells positive for Ki-67 (green) scarcely existed in the dorsal-posterior putamen. Scale bar: 100 μm. (C) Quantitative analysis of the ratio of Ki-67+ cells to the total number of cells in 3 groups of striatum (MSC-DP grafted, sham operated, nonaffected). See also Supplemental Tables 1 and 2 for the results of blood tests for biochemical and tumor markers.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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