ArticleExperimental & molecular medicine2025
Generation of hypoimmunogenic universal iPS cells through HLA-type gene knockout.
Article in Experimental & molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Induced Pluripotent Stem Cell-Derived Small-Diameter Vascular Grafts: Scaffold Design, Immune Engineering, and Clinical Translation.Journal of cellular physiology · 2026Review
- Engineering autoimmune disease models using organoids: Harnessing microenvironmental engineering for precision medicine and immunological recapitulation.Bioengineering & translational medicine · 2026Review
- Article
- Blood Pharming of Red Cells.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2026Review
- Cell-based regenerative interventions in Parkinson's disease: Overcoming pharmacological limitations.Acta pharmaceutica Sinica. B · 2026Review
- Tracheal Regeneration: Recent Progress in the Application of Stem Cells in Tracheal Bioengineering.International journal of molecular sciences · 2026Review
- Advances in the differentiation of induced pluripotent stem cells into vascular cells for the treatment of diabetic microvascular disease.Cardiovascular diabetology · 2026Review
- The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.Frontiers in immunology · 2026Review
- Progressing Regenerative Medicine: Integrating Bioprinting Platforms for Stem Cell Applications.Stem cells international · 2026Review
- Modeling myeloid cell development in health and disease using induced pluripotent stem cells.Frontiers in immunology · 2026Review
- Immunogenicity of Fetal Liver-Derived Progenitor and Stem Cells: Expression of MHC Molecules.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Deep immune-phenotyping of HLA-homozygous iPS-cardiomyocytes by spectral flow cytometry.Frontiers in immunology · 2026Article
- Revisiting macrophage metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: mechanisms, regulation, and therapeutic breakthroughs.Frontiers in immunology · 2026Review
- Novel developments in retinal regeneration: Advances and future outlooks in stem cell therapy.World journal of stem cells · 2025Review
- Applications of Modern Cell Therapies: The Latest Data in Ophthalmology.Life (Basel, Switzerland) · 2025Review
- Hypoimmune stem cells and islets: hype or a true breakthrough in diabetes treatment?Cellular & molecular biology letters · 2025Review
- Developing stem cells for corneal disease: recent developments and future perspectives.Regenerative medicine · 2025Review
- Recent advances in stem cell-based therapies for type 1 diabetes: A glimpse into the future.Biomolecules & biomedicine · 2025Review
- Research progress of stem cells in the treatment of atherosclerosis.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
12 authors.
Funding
Abstract
Hypoimmunogenic universal induced pluripotent stemn (iPS) cells were generated through the targeted disruption of key genes, including human leukocyte antigen (HLA)-A, HLA-B and HLA-DR alpha (DRA), using the CRISPR-Cas9 system. This approach aimed to minimize immune recognition and enhance the potential of iPS cells for allogeneic therapy. Heterozygous iPS cells were used for guide RNA design and validation to facilitate the knockout (KO) of the HLA-A, HLA-B and HLA-DRA genes. The electroporation of iPS cells using the selected guide RNAs enabled the generation of triple-KO iPS cells, followed by single-cell cloning for clone selection. Clone A7, an iPS cell with targeted KOs of the HLA-A, HLA-B and HLA-DRA genes, was identified as the final candidate. Messenger RNA analysis revealed robust expression of pluripotency markers, such as octamer-binding transcription factor 4, sex-determining region Y box 2, Krüppel-like factor 4, Lin-28 homolog A and Nanog homeobox, while protein expression assays confirmed the presence of octamer-binding transcription factor 4, stage-specific embryonic antigen 4, Nanog homeobox and tumor rejection antigen 1-60. A karyotype examination revealed no anomalies, and three-germ layer differentiation assays confirmed the differentiation potential. After interferon gamma stimulation, the gene-corrected clone A7 lacked HLA-A, HLA-B and HLA-DR protein expression. Immunogenicity testing further confirmed the hypoimmunogenicity of clone A7, which was evidenced by the absence of proliferation in central memory T cells and effector memory T cells. In conclusion, clone A7, a triple-KO iPS cell clone that demonstrates immune evasion properties, retained its intrinsic iPS cell characteristics and exhibited no immunogenicity.
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