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Transplantation therapy using induced pluripotent stem cell (iPS) cell-derived dopamine (DA) progenitors for Parkinson's disease (PD) has attracted attention as an innovative treatment to restore DA neurons in PD, which leads to the improvement of motor disturbance. iPS cells are multipotent stem cells with very high proliferation activity, created by reprogramming mature somatic cells through the transduction of four transcription factors. Relative to fetal midbrain DA neurons, iPS cells have advantages in terms of ethical aspects and availability. On the other hand, the most serious concern associated with therapies with ES/iPS cells is the risk of tumor growth that is caused by the proliferation of undifferentiated ES/iPS cells. Human ES cells that differentiate into DA neurons have been shown to form teratomas. Another concern is graft-induced dyskinesia (GID). GID, which is likely caused by several factors including contamination with serotonergic neurons, developed in the recipients of fetal ventral midbrain (VM) in randomized controlled trials. To enrich the DA progenitor cells and eliminate unwanted cells, a protocol for sorting midbrain DA neurons with antibodies against CORIN, a marker for floor plates, was developed. CORIN-sorted dopamine progenitors were transplanted into the bilateral putamina of MPTP-treated Parkinson models of cynomolgus monkeys, resulting in 18F-DOPA PET-positive graft formation and motor improvement without tumor formation two years after the surgeries. Very recently, a phase I/II trial of iPSC-derived, CORIN-sorted dopaminergic cells for Parkinson's disease was completed (The Kyoto Trial) (Takahashi, 2020; Sawamoto et al., 2025) [1,2]. Based on the results of the trial, we would like to discuss the current status and future perspectives of iPS cell therapy for PD.
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