Universal and hypoimmunogenic pluripotent stem cells for clinical usage

Tzu Cheng Sung, Kailibinuer Maitiruze, Jiandong Pan, Jian Gong, Yongheng Bai, Xiaodong Pan, Akon Higuchi

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


It is urgent to prepare and store large numbers of clinical trial grade human pluripotent stem (hPS) cells for off-the-shelf use in stem cell therapies. However, stem cell banks, which store off-the-shelf stem cells, need financial support and large amounts of technicians for daily cell maintenance. Therefore, it is valuable to create “universal” or “hypoimmunogenic” hPS cells with genome editing engineering by knocking in or out immune-related genes. Only a small number of universal or hypoimmunogenic hPS cell lines should be needed to store for off-the-shelf usage and reduce the large amounts of instruments, consumables and technicians. In this article, we consider how to create hypoimmunogenic or universal hPS cells as well as the demerits of the technology. β2-Microglobulin-knockout hPS cells did not harbor human leukocyte antigen (HLA)-expressing class I cells but led to the activation of natural killer cells. To escape the activities of macrophages and natural killer cells, homozygous hPS cells having a single allele of an HLA class I gene, such as HLA-C, were proposed. Major HLA class Ia molecules were knocked out, and CD47, HLA-G and PD-L1 were knocked in hPS cells utilizing CRISPR/Cas9 genome editing. Finally, some researchers are trying to generate universal hPS cells without genome editing. The cells evaded the activation of not only T cells but also macrophages and natural killer cells. These universal hPS cells have high potential for application in cell therapy.

Original languageEnglish
Title of host publicationProgress in Molecular Biology and Translational Science
EditorsAkon Higuchi, Yinghong Zhou, Shih-Hwa Chiou
PublisherElsevier B.V.
Number of pages26
ISBN (Print)9780443134111
StatePublished - Jan 2023

Publication series

NameProgress in Molecular Biology and Translational Science
ISSN (Print)1877-1173
ISSN (Electronic)1878-0814


  • Cell therapy
  • Human leukocyte antigen
  • Hypoimmunogenic hPS cells
  • Immune privilege
  • Off-the-shelf cells
  • Universal hPS cells


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