符合GMP的iPS细胞系在细胞替代和癌症免疫疗法的新一套分化工作流中表现出广泛的可塑性
Daniel Terheyden-Keighley1, Melanie Hühne1, Thomas Berger1
1Catalent Düsseldorf GmbH, 40764 Langenfeld, Germany.
Stem cells translational medicine
|July 23, 2024
概括
我们生成了第一个良好制造实践 (GMP) 诱导的多能干细胞 (iPSC) 银行,并为细胞治疗应用开发了符合GMP的工作流. 这些进步改善了基因向和分化到关键细胞类型,如RPE,MSC,心肌细胞和免疫细胞.
科学领域:
- 干细胞生物学 干细胞生物学
- 细胞治疗学 细胞治疗学
- 生物技术是生物技术.
背景情况:
- 诱导多能干细胞 (iPSC) 对细胞疗法具有很大的前景,但由于良好的制造实践 (GMP) 规定,在制造质量和一致性方面面临挑战.
- 可访问的符合GMP的iPSC线路的稀缺性阻碍了它们的临床转化.
- 开发强大的GMP生产工作流程对于推进基于iPSC的疗法至关重要.
研究的目的:
- 建立第一个符合GMP的诱导多能干细胞 (iPSC) 银行.
- 开发符合GMP的工作流程,以增强基因向和iPSC的定向差异化.
- 创建多功能平台,用于产生各种细胞类型的治疗应用.
主要方法:
- 建立了一个生产工作流程,用于从带血中生成符合GMP的iPSC细胞库.
- 开发了与GMP兼容的基因向,视网膜色素上皮质 (RPE) 生成,介酶体 stromal 细胞 (MSC) 扩张,心肌细胞分化和免疫细胞诱导的协议.
- 利用通用免疫细胞诱导平台产生多能造血细胞前体.
主要成果:
- 产生了第一个符合GMP的iPSC细胞库,满足全面释放规范,具有低突变负载.
- 实现了基因向效率的提高,并指导分化为RPE,MSC,心肌细胞 (>95%纯度),以及各种免疫细胞 (巨细胞,T细胞,NK细胞).
- 证明了从iPSC衍生的前体中NK细胞的几千倍扩张的源细胞独立方法.
结论:
- 开发的GMP iPSC线和操纵平台为细胞治疗和基础研究提供了宝贵的资源.
- 改进的符合良好生产准则的工作流程有助于有效地产生多样化,高质量的细胞类型,用于治疗.
- 这些进展解决了关键的制造挑战,为iPSC技术的更广泛的临床应用铺平了道路.
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