Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
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.
| Errataetall: |
CommentIn: Cell Stem Cell. 2024 Jan 4;31(1):5-6. - PMID 38181750 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Cell stem cell - 31(2024), 1 vom: 04. Jan., Seite 25-38.e8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Park, Sanghyun [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.01.2024 Date Revised 22.03.2024 published: Print-Electronic CommentIn: Cell Stem Cell. 2024 Jan 4;31(1):5-6. - PMID 38181750 Citation Status MEDLINE |
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| doi: |
10.1016/j.stem.2023.11.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Lee, Jae Souk |e verfasserin |4 aut | |
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| 700 | 1 | |a Oh, Young Woo |e verfasserin |4 aut | |
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