Abstract
BackgroundCell 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.MethodsThe 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.ResultsRPE 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.ConclusionsThis 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.
Highlights
Cell therapy is proposed to be a potential treatment for Parkinson’s disease (PD)
After being grafted into the brain caudate putamen of monkeys with chemically induced PD, retinal pigment epithelial (RPE)-grafted PD monkeys showed significant improvement of clinical conditions, due to the fact that some transplanted RPE cells became positive for tyrosine hydroxylase
Isolation and characterization of RPE cell lines from adult human eye tissues RPE tissue was isolated from frozen posterior eye tissue, and tissue debris was cultured in serum-free conditional media
Summary
Cell therapy is proposed to be a potential treatment for Parkinson’s disease (PD). PD is caused by the loss of dopamine (DA)-producing neurons in the substantia nigra pars compacta (Hardy, 2010). Patients with PD are currently treated with a variety of pharmacological drugs, including levodopa, dopamine (2019) 25:9 agonists, and monoamine oxidase B inhibitors. Levodopa is the most effective drug, but unwanted side effects are often observed, including fluctuations in the symptoms of PD, and dyskinesias (Chapuis et al, 2005; Isacson, 2004). In spite of improvements in symptom management, all of these therapies cannot stop disease progression (Krack et al, 2003)
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