Differentiation of adult human retinal pigment epithelial cells into dopaminergic-like cells in vitro and in the recipient monkey brain

成人视网膜色素上皮细胞在体外和受体猴脑中向多巴胺样细胞的分化

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作者:Sha Li, Han Zhang, Aifang Wang, Yan Liu, Houqi Liu, Feng Yue, Xianmixinuer Abulaiti, Caiqiao Zhang, Lingsong Li

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

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.

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.

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