基于诱导多能干细胞（iPSC）的细胞治疗应用显得非常有前景，同时也充满挑战。在制造 iPSC 及其差异化后代时，良好生产规范 (GMP) 法规对质量和一致性提出了必要但苛刻的要求。鉴于缺乏可用的 GMP iPSC 细胞系，我们建立了相应的生产工作流程来生成第一套合规细胞库。因此，这些品系符合一套全面的发布规范，并且，例如，显示出较低的总体突变负荷，反映了它们的新生儿来源——脐带血。基于这些 iPSC 系，我们还开发了一套 GMP 兼容的工作流程，能够以极大提高的效率改进基因靶向，并定向分化为关键细胞类型：用于生成视网膜色素上皮 (RPE) 的新方案具有高度简单性和效率。源自 iPSC 的间充质基质细胞 (MSC) 显示出出色的扩增能力。完全优化的心肌细胞分化方案的特点是批次间一致性特别高，纯度高于 95%。最后，我们介绍了一个通用的免疫细胞诱导平台，可将 iPSC 转化为多能前体细胞。这些造血前体细胞可以选择性地被刺激成为巨噬细胞、T 细胞或自然杀伤 (NK) 细胞。 NK 细胞分化时培养条件的改变诱导了数千倍的扩增，这为以不依赖于饲养细胞的方法放大这种关键细胞类型开辟了前景。总而言之，这些细胞系和改进的操作平台将在细胞治疗和基础研究中具有广泛的用途。© 作者 2024。由牛津大学出版社出版。

Cell therapeutic applications based on induced pluripotent stem cells (iPSCs) appear highly promising and challenging at the same time. Good manufacturing practice (GMP) regulations impose necessary yet demanding requirements for quality and consistency when manufacturing iPSCs and their differentiated progeny. Given the scarcity of accessible GMP iPSC lines, we have established a corresponding production workflow to generate the first set of compliant cell banks. Hence, these lines met a comprehensive set of release specifications and, for instance, displayed a low overall mutation load reflecting their neonatal origin, cord blood. Based on these iPSC lines, we have furthermore developed a set of GMP-compatible workflows enabling improved gene targeting at strongly enhanced efficiencies and directed differentiation into critical cell types: A new protocol for the generation of retinal pigment epithelium (RPE) features a high degree of simplicity and efficiency. Mesenchymal stromal cells (MSCs) derived from iPSCs displayed outstanding expansion capacity. A fully optimized cardiomyocyte differentiation protocol was characterized by a particularly high batch-to-batch consistency at purities above 95%. Finally, we introduce a universal immune cell induction platform that converts iPSCs into multipotent precursor cells. These hematopoietic precursors could selectively be stimulated to become macrophages, T cells, or natural killer (NK) cells. A switch in culture conditions upon NK-cell differentiation induced a several thousand-fold expansion, which opens up perspectives for upscaling this key cell type in a feeder cell-independent approach. Taken together, these cell lines and improved manipulation platforms will have broad utility in cell therapy as well as in basic research.© The Author(s) 2024. Published by Oxford University Press.