ArticleStem cell research & therapy2024
Hypoimmunogenic human iPSCs expressing HLA-G, PD-L1, and PD-L2 evade innate and adaptive immunity.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Cellularized Skin Substitute Bioengineering for Regenerative Medicine: Cell Sources, Culture Strategies, and Transition Toward Defined, Xeno-Free Culture Systems.Advanced healthcare materials · 2026Review
- Stem cell-based therapies for type 1 diabetes: Progress in differentiation, clinical translation, and immune protection.Animal models and experimental medicine · 2026Review
- Advanced in vitro cardiac models for drug evaluation: integration of organoids, engineered tissues, and microphysiological systems.Microsystems & nanoengineering · 2026Review
- Evaluating iPSC-based interventions for diabetes: a systematic review and meta-analysis.Diabetology & metabolic syndrome · 2026Article
- Immune-evasive stem cells: engineering tolerance and reprogramming microenvironments for regenerative therapy.Stem cell research & therapy · 2026Review
- Skin Organoids in Diabetic Chronic Wounds: Current Status and Future Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Modeling myeloid cell development in health and disease using induced pluripotent stem cells.Frontiers in immunology · 2026Review
- HLA incompatibility mitigation strategies in off-the-shelf cancer immunotherapies: clinical implications and a practical framework for strategy selection and combination.Frontiers in immunology · 2026Article
- Deep immune-phenotyping of HLA-homozygous iPS-cardiomyocytes by spectral flow cytometry.Frontiers in immunology · 2026Article
- Dendritic cell progenitors engineered to express extracellular-vesicle-internalizing receptors enhance cancer immunotherapy in mouse models.Nature communications · 2025Article
- Hypoimmune stem cells and islets: hype or a true breakthrough in diabetes treatment?Cellular & molecular biology letters · 2025Review
- Stem Cell Therapy in Ischemic Heart Failure.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025Review
- Allogenic Transplantation of RPE Strips Lacking MHC Class II Can Avoid Rejection in Nonhuman Primate Eyes.Investigative ophthalmology & visual science · 2025Article
- Review
- Personalized Stem Cell-Based Regeneration in Spinal Cord Injury Care.International journal of molecular sciences · 2025Review
- Recent advances in stem cell-based therapies for type 1 diabetes: A glimpse into the future.Biomolecules & biomedicine · 2025Review
- Antitumor effects of natural killer cells derived from gene-engineered human-induced pluripotent stem cells on hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2025Article
- Harnessing the immunomodulatory properties of HLA-G for advanced immunotherapies.Frontiers in immunology · 2025Review
- From Edmonton to Lantidra and beyond: immunoengineering islet transplantation to cure type 1 diabetes.Frontiers in transplantation · 2025Review
- Clinical translation of human iPSC technologies: advances, safety concerns, and future directions.Frontiers in cell and developmental biology · 2025Review
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14 authors.
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Abstract
backgroundThe human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate source of stem cells for regenerative medicine. The major challenge of allogeneic hiPSC-derived cell products is their immunogenicity. The hypoimmunogenic cell strategy is allogenic cell therapy without using immune suppressants. Advances in gene engineering technology now permit the generation of hypoimmunogenic cells to avoid allogeneic immune rejection. In this study, we generated a hypoimmunogenic hiPSC (HyPSC) clone that had diminished expression of human leukocyte antigen (HLA) class Ia and class II and expressed immune checkpoint molecules and a safety switch.
methodsFirst, we generated HLA class Ia and class II double knockout (HLA class Ia/II DKO) hiPSCs. Then, a HyPSC clone was generated by introducing exogenous β-2-microglobulin (B2M), HLA-G, PD-L1, and PD-L2 genes, and the Rapamycin-activated Caspase 9 (RapaCasp9)-based suicide gene as a safety switch into the HLA class Ia/II DKO hiPSCs. The characteristics and immunogenicity of the HyPSCs and their derivatives were analyzed.
resultsWe found that the expression of HLA-G on the cell surface can be enhanced by introducing the exogenous HLA-G gene along with B2M gene into HLA class Ia/II DKO hiPSCs. The HyPSCs retained a normal karyotype and had the characteristics of pluripotent stem cells. Moreover, the HyPSCs could differentiate into cells of all three germ layer lineages including CD45
conclusionThe HLA class Ia/II DKO hiPSCs armed with HLA-G, PD-L1, PD-L2, and RapaCasp9 molecules are a potential source of stem cells for allogeneic transplantation.
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