小柯机器人

韩国延世大学医学院Dong-Wook Kim等研究人员合作完成用于帕金森病临床试验的多巴胺能祖细胞临床前和剂量范围评估。该研究于2023年12月11日在线发表于国际一流学术期刊《细胞—干细胞》。

研究人员表示，人类胚胎干细胞（hESC）衍生的中脑多巴胺能（mDA）细胞移植是治疗帕金森病（PD）的一种前景广阔的策略。

研究人员介绍了在严格的良好生产规范（GMP）条件下从临床级hESC大规模衍生出高纯度mDA原代细胞的过程。研究人员还在符合良好实验室规范（GLP）的设施中评估了这些细胞在免疫缺陷大鼠体内的毒性、生物分布和致瘤性。将不同剂量的mDA祖细胞移植到半帕金森病大鼠体内，观察到了显著的剂量依赖性行为改善，最小有效剂量范围为5000-10000 mDA祖细胞。

这些结果为确定人体临床试验的低细胞剂量（315万个细胞）提供了启示。基于这些结果，韩国食品药品安全部批准了针对帕金森病细胞疗法的1/2a期临床试验，治疗帕金森病患者的临床试验已经开始。

附：英文原文

Title: Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease

Author: Sanghyun Park, Chan Wook Park, Jang Hyeon Eom, Mi-Young Jo, Hye-Jin Hur, Sung Kyoung Choi, Jae Souk Lee, Seung Taek Nam, Ki-Sang Jo, Young Woo Oh, Jungil Lee, Sieun Kim, Do-Hun Kim, Chul-Yong Park, Su Jin Kim, Ho-Young Lee, Myung Soo Cho, Dae-Sung Kim, Dong-Wook Kim

Issue&Volume: 2023-12-11

Abstract: 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.

DOI: 10.1016/j.stem.2023.11.009

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00401-0

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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