Off-the-Shelf, Immune-Compatible Human Embryonic Stem Cells Generated Via CRISPR-Mediated Genome Editing
Open Access
- 9 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Stem Cell Reviews and Reports
- Vol. 17 (3), 1053-1067
- https://doi.org/10.1007/s12015-020-10113-7
Abstract
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. Graphical AbstractKeywords
Funding Information
- Ministry of Science ICT and Future Planning (2018M3A9H2021665, 2018M3A9H2021653)
- Institute for Basic Science (IBS-R021-D1)
This publication has 47 references indexed in Scilit:
- Toward eliminating HLA class I expression to generate universal cells from allogeneic donorsBlood, 2013
- Six-locus high resolution HLA haplotype frequencies derived from mixed-resolution DNA typing for the entire US donor registryHuman Immunology, 2013
- HLA Engineering of Human Pluripotent Stem CellsMolecular Therapy, 2013
- Low Incidence of DNA Sequence Variation in Human Induced Pluripotent Stem Cells Generated by Nonintegrating Plasmid ExpressionCell Stem Cell, 2012
- Somatic coding mutations in human induced pluripotent stem cellsNature, 2011
- Evaluation of 28 Human Embryonic Stem Cell Lines for Use as Unrelated Donors in Stem Cell Therapy: Implications of HLA and ABO GenotypesCell Transplantation, 2010
- Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney TransplantationJournal of the American Society of Nephrology, 2010
- HLA-A, -B, -DRB1 allele frequencies and haplotypic association from DNA typing data of 7096 Korean cord blood unitsTissue Antigens, 2010
- Human Embryonic Stem Cells Possess Immune‐Privileged PropertiesThe International Journal of Cell Cloning, 2004
- Nonsense-mediated mRNA decay: terminating erroneous gene expressionCurrent Opinion in Cell Biology, 2004