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Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced., Competing Interests: Declaration of interests D.-W.K. is a chief technology officer of S. Biomedics Co., Ltd. J.H.E., M.-Y.J., H.-J.H., S.K.C., S.T.N., K.-S.J., D.-H.K., C.-Y.P., and M.S.C. are currently employed at S. Biomedics Co., Ltd. We have patents related to this work. 1. Title: method for inducing differentiation of stem cells into dopaminergic neural precursor cells, patent number: 102392133(KR), 11655450(US), 07152050(JP), and 2020202273(AU). 2. Title: efficient and universal method for neural differentiation of human pluripotent stem cells, patent number: 101168053(KR), 08551783(US), 05756019(JP), and 02502987(EP)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)