全面性和低免疫性多能干细胞用于临床使用
Tzu-Cheng Sung1, Kailibinuer Maitiruze1, Jiandong Pan1
1State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
Progress in molecular biology and translational science
|September 7, 2023
概括
创建通用的低免疫性人类多能干细胞 (hPS) 对可访问的细胞疗法至关重要. 设计这些细胞减少了对干细胞银行大量资源和技术人员的需求.
科学领域:
- 干细胞生物学 干细胞生物学
- 免疫学 免疫学 免疫学
- 基因工程是一种基因工程.
背景情况:
- 临床试验级人类多能干细胞 (hPS) 需要用于现成的细胞疗法.
- 目前的干细胞银行需要大量的资金支持和技术人员来维护细胞.
- 开发通用或低免疫性hPS细胞可以简化细胞治疗物流.
研究的目的:
- 探索制造低免疫性或通用hPS细胞的方法.
- 为此目的讨论基因组编辑技术的优缺点.
主要方法:
- 使用CRISPR/Cas9进行基因编辑,以淘汰与免疫相关的基因 (例如β2-微球蛋白,HLA类Ia).
- 在免疫逃避基因 (例如CD47,HLA-G,PD-L1) 中敲击.
- 调查没有基因组编辑的替代方法.
主要成果:
- β2-微球蛋白淘汰hPS细胞缺乏HLA类I,但激活了自然杀手细胞.
- 涉及 homozygous 单个 HLA I 类等位基因表达的策略被提出以逃避免疫细胞.
- 工程 hPS 细胞与被淘汰的主要 HLA 类 Ia 和被淘汰的 CD47,HLA-G 和 PD-L1 显示出有希望.
- 没有基因组编辑的通用hPS细胞证明了对T细胞,巨细胞和自然杀手细胞的逃避.
结论:
- 全面性低免疫性hPS细胞具有促进细胞治疗应用的巨大潜力.
- 基因组编辑和新的方法是开发现成干细胞解决方案的关键.
- 降低免疫性对于hPS基于细胞的疗法的广泛临床使用至关重要.
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