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Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing

Human embryonic stem cells (hESCs) hold promise in regenerative medicine but allogeneic immune rejections caused by highly polymorphic human leukocyte antigens (HLAs) remain a barrier to their clinical applications. Here, we used a CRISPR/Cas9-mediated HLA-editing strategy to generate a variety of H...

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Autores principales: Kim, Annie, Lee, Kun-Gu, Kwon, Yeongbeen, Lee, Kang-In, Yang, Heung-Mo, Habib, Omer, Kim, Jihun, Kim, Sang-Tae, Kim, Sung Joo, Kim, Jin-Soo, Hwang, Dong-Youn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166669/
https://www.ncbi.nlm.nih.gov/pubmed/33423156
http://dx.doi.org/10.1007/s12015-020-10113-7
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author Kim, Annie
Lee, Kun-Gu
Kwon, Yeongbeen
Lee, Kang-In
Yang, Heung-Mo
Habib, Omer
Kim, Jihun
Kim, Sang-Tae
Kim, Sung Joo
Kim, Jin-Soo
Hwang, Dong-Youn
author_facet Kim, Annie
Lee, Kun-Gu
Kwon, Yeongbeen
Lee, Kang-In
Yang, Heung-Mo
Habib, Omer
Kim, Jihun
Kim, Sang-Tae
Kim, Sung Joo
Kim, Jin-Soo
Hwang, Dong-Youn
author_sort Kim, Annie
collection PubMed
description Human embryonic stem cells (hESCs) hold promise in regenerative medicine but allogeneic immune rejections caused by highly polymorphic human leukocyte antigens (HLAs) remain a barrier to their clinical applications. Here, we used a CRISPR/Cas9-mediated HLA-editing strategy to generate a variety of HLA homozygous-like hESC lines from pre-established hESC lines. We edited four pre-established HLA-heterozygous hESC lines and created a mini library of 14 HLA-edited hESC lines in which single HLA-A and HLA-B alleles and both HLA-DR alleles are disrupted. The HLA-edited hESC derivatives elicited both low T cell- and low NK cell-mediated immune responses. Our library would cover about 40% of the Asian-Pacific population. We estimate that HLA-editing of only 19 pre-established hESC lines would give rise to 46 different hESC lines to cover 90% of the Asian-Pacific population. This study offers an opportunity to generate an off-the-shelf HLA-compatible hESC bank, available for immune-compatible cell transplantation, without embryo destruction. [Figure: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12015-020-10113-7.
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spelling pubmed-81666692021-06-03 Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing Kim, Annie Lee, Kun-Gu Kwon, Yeongbeen Lee, Kang-In Yang, Heung-Mo Habib, Omer Kim, Jihun Kim, Sang-Tae Kim, Sung Joo Kim, Jin-Soo Hwang, Dong-Youn Stem Cell Rev Rep Article Human embryonic stem cells (hESCs) hold promise in regenerative medicine but allogeneic immune rejections caused by highly polymorphic human leukocyte antigens (HLAs) remain a barrier to their clinical applications. Here, we used a CRISPR/Cas9-mediated HLA-editing strategy to generate a variety of HLA homozygous-like hESC lines from pre-established hESC lines. We edited four pre-established HLA-heterozygous hESC lines and created a mini library of 14 HLA-edited hESC lines in which single HLA-A and HLA-B alleles and both HLA-DR alleles are disrupted. The HLA-edited hESC derivatives elicited both low T cell- and low NK cell-mediated immune responses. Our library would cover about 40% of the Asian-Pacific population. We estimate that HLA-editing of only 19 pre-established hESC lines would give rise to 46 different hESC lines to cover 90% of the Asian-Pacific population. This study offers an opportunity to generate an off-the-shelf HLA-compatible hESC bank, available for immune-compatible cell transplantation, without embryo destruction. [Figure: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12015-020-10113-7. Springer US 2021-01-09 2021 /pmc/articles/PMC8166669/ /pubmed/33423156 http://dx.doi.org/10.1007/s12015-020-10113-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kim, Annie
Lee, Kun-Gu
Kwon, Yeongbeen
Lee, Kang-In
Yang, Heung-Mo
Habib, Omer
Kim, Jihun
Kim, Sang-Tae
Kim, Sung Joo
Kim, Jin-Soo
Hwang, Dong-Youn
Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing
title Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing
title_full Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing
title_fullStr Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing
title_full_unstemmed Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing
title_short Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing
title_sort off-the-shelf, immune-compatible human embryonic stem cells generated via crispr-mediated genome editing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166669/
https://www.ncbi.nlm.nih.gov/pubmed/33423156
http://dx.doi.org/10.1007/s12015-020-10113-7
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