Abstract
Induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson’s disease (PD). The regulatory criteria for the clinical application of these therapies, however, have not been established. Here we show the results of our pre-clinical study, in which we evaluate the safety and efficacy of dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line. We confirm the characteristics of DAPs by in vitro analyses. We also verify that the DAP population include no residual undifferentiated iPSCs or early neural stem cells and have no genetic aberration in cancer-related genes. Furthermore, in vivo studies using immunodeficient mice reveal no tumorigenicity or toxicity of the cells. When the DAPs are transplanted into the striatum of 6-OHDA-lesioned rats, the animals show behavioral improvement. Based on these results, we started a clinical trial to treat PD patients in 2018.
Highlights
Induced pluripotent stem cell-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson’s disease (PD)
We have preserved the Induced pluripotent stem cell (iPSC) in hundreds of frozen vials as one lot
We extensively investigated mutations in the 686 cancerrelated genes listed in the Catalog of Somatic Mutations In Cancer (COSMIC) Census (COSMIC version 83)
Summary
Induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson’s disease (PD). When the DAPs are transplanted into the striatum of 6OHDA-lesioned rats, the animals show behavioral improvement Based on these results, we started a clinical trial to treat PD patients in 2018. Culture protocols that induce authentic midbrain dopaminergic (DA) neurons from human PSCs have already been established by several research groups, and the DA neurons have been proven safe and effective in rodent[6,7] and primate[8] PD models These results suggest that PSC-derived DA neurons can contribute to the treatment of PD. We confirm the safety and efficacy of iPSC-derived DAPs for clinical trials
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