Universal and hypoimmunogenic pluripotent stem cells for clinical usage

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

研究成果: 書貢獻/報告類型篇章同行評審

摘要

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.

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主出版物標題Progress in Molecular Biology and Translational Science
編輯Akon Higuchi, Yinghong Zhou, Shih-Hwa Chiou
發行者Elsevier B.V.
頁面271-296
頁數26
ISBN(列印)9780443134111
DOIs
出版狀態已出版 - 1月 2023

出版系列

名字Progress in Molecular Biology and Translational Science
199
ISSN(列印)1877-1173
ISSN(電子)1878-0814

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