There is a need to store very large numbers of conventional human pluripotent stem cell (hPSC) lines for their off‐the‐shelf usage in stem cell therapy. Therefore, it is valuable to generate “universal” or “hypoimmunogenic” hPSCs with gene‐editing technology by knocking out or in immune‐related genes. A few universal or hypoimmunogenic hPSC lines should be enough to store for their off‐the‐shelf usage. Here, we overview and discuss how to prepare universal or hypoimmunogenic hPSCs and their disadvantages. β2‐Microglobulin‐knockout hPSCs did not harbour human leukocyte antigen (HLA)‐expressing class I cells but rather activated natural killer (NK) cells. To avoid NK cell and macrophage activities, homozygous hPSCs expressing a single allele of an HLA class I molecule, such as HLA‐C, were developed. Major HLA class I molecules were knocked out, and PD‐L1, HLA‐G and CD47 were knocked in hPSCs using CRISPR/Cas9 gene editing. These cells escaped activation of not only T cells but also NK cells and macrophages, generating universal hPSCs.

中文翻译：

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通用和低免疫原性人类多能干细胞的产生

需要储存非常大量的传统人类多能干细胞 (hPSC) 系，以便在干细胞治疗中现成使用。因此，利用基因编辑技术通过敲除免疫相关基因或在免疫相关基因中产生“通用”或“低免疫原性”hPSCs是有价值的。一些通用的或低免疫原性的 hPSC 系应该足以储存它们的现成使用。在这里，我们概述和讨论如何制备通用或低免疫原性 hPSC 及其缺点。敲除 β2 微球蛋白的 hPSC 不含有表达人类白细胞抗原 (HLA) 的 I 类细胞，而是含有活化的自然杀伤 (NK) 细胞。为了避免 NK 细胞和巨噬细胞活动，开发了表达 HLA I 类分子（如 HLA-C）的单个等位基因的纯合 hPSC。主要的 HLA I 类分子被敲除，使用 CRISPR/Cas9 基因编辑在 hPSC 中敲除 PD-L1、HLA-G 和 CD47。这些细胞不仅逃避了 T 细胞的激活，还逃避了 NK 细胞和巨噬细胞的激活，从而产生了通用的 hPSC。