机构：[1]College of Animal Sciences, Zhejiang University, Hangzhou 310029, China.[2]Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.[3]University of Chinese Academy of Sciences, Beijing 100049, China.[4]School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.[5]Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 201210, China.[6]Research Center of Developmental Biology, Second Military Medical University, Shanghai 200433, China.[7]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.首都医科大学宣武医院神经生物学研究室[8]Henan Key laboratory of Stem Cell Differentiation and Modification, Henan Provincial People’s Hospital, Henan University and Zhengzhou University, Zhengzhou, China.
Background: Cell therapy is proposed to be a potential treatment for Parkinson's disease (PD). Although fetal retinal pigment epithelial (RPE) cells have been tested in trials for treating PD patients, controversy has been raised over the issue of whether such cells can be reprogrammed into dopamine-producing cells for therapeutic efficacy. Here, we aim to investigate whether adult human RPE cells can be reprogrammed into dopamine-producing cells both in vitro and in the recipient monkey brain. Methods: The RPE layer was isolated from frozen posterior eyeball tissue after penetrating keratoplasty surgery. The tumorigenicity of RPE cells was examined by G-banding and a tumor formation assay in nude mice. Immunogenicity was measured using a one-way mixed lymphocyte reaction (MLR) assay. Dopamine-production in chemically reprogrammed RPE cells was measured by HPLC. Finally, RPE cells were grafted into the brains of monkeys with MPTP-induced PD in order to investigate the potential of such cells treating PD patients in the future. Results: RPE cell lines have been successively established from adult human eye tissues. Such cells can be chemically reprogrammed into dopamine-producing cells in vitro. Moreover, after being grafted into the brain caudate putamen of monkeys with MPTP-induced PD, RPE cells became tyrosine hydroxylase-positive cells, and recipient PD monkeys showed significant improvement of clinical conditions. Conclusions: This preclinical study using a primate model indicates that human adult RPE cells could be a potential cell source for the treatment of PD in the future.
基金：
863 Program [2015AA020303]; Ministry of Science and Technology of China; Foundation of Henan Provincial People's Hospital [Y765001H21]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|2 区医学
小类|3 区生化与分子生物学3 区细胞生物学3 区医学：研究与实验
最新[2025]版：
大类|2 区医学
小类|2 区生化与分子生物学2 区细胞生物学2 区医学：研究与实验
JCR分区：
出版当年[2017]版：
Q2BIOCHEMISTRY & MOLECULAR BIOLOGYQ2MEDICINE, RESEARCH & EXPERIMENTALQ2CELL BIOLOGY
最新[2023]版：
Q1BIOCHEMISTRY & MOLECULAR BIOLOGYQ1MEDICINE, RESEARCH & EXPERIMENTALQ2CELL BIOLOGY
第一作者机构：[1]College of Animal Sciences, Zhejiang University, Hangzhou 310029, China.
通讯作者：
通讯机构：[2]Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.[3]University of Chinese Academy of Sciences, Beijing 100049, China.[4]School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.[5]Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 201210, China.[8]Henan Key laboratory of Stem Cell Differentiation and Modification, Henan Provincial People’s Hospital, Henan University and Zhengzhou University, Zhengzhou, China.
推荐引用方式(GB/T 7714)：
Sha Li,Han Zhang,Aifang Wang,et al.Differentiation of adult human retinal pigment epithelial cells into dopaminergic-like cells in vitro and in the recipient monkey brain[J].MOLECULAR MEDICINE.2019,25(1):9.doi:10.1186/s10020-019-0076-3.
APA：
Sha Li,Han Zhang,Aifang Wang,Yan Liu,Houqi Liu...&Lingsong Li.(2019).Differentiation of adult human retinal pigment epithelial cells into dopaminergic-like cells in vitro and in the recipient monkey brain.MOLECULAR MEDICINE,25,(1)
MLA：
Sha Li,et al."Differentiation of adult human retinal pigment epithelial cells into dopaminergic-like cells in vitro and in the recipient monkey brain".MOLECULAR MEDICINE 25..1(2019):9
医学