Generation of universal and hypoimmunogenic human pluripotent stem cells

Qingsong Ye, Tzu Cheng Sung, Jen Ming Yang, Qing Dong Ling, Yan He, Akon Higuchi

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


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.

Original languageEnglish
Article numbere12946
JournalCell Proliferation
Issue number12
StatePublished - Dec 2020


  • regenerative medicine
  • stem cells


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