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Immune-evasive human islet-like organoids ameliorate diabetes
Open accessAbstract
Islets derived from stem cells hold promise as a therapy for insulin-dependent diabetes, but there remain challenges towards achieving this goal 1-6. Here we generate human islet-like organoids (HILOs) from induced pluripotent stem cells and show that non-canonical WNT4 signalling drives the metabolic maturation necessary for robust ex vivo glucose-stimulated insulin secretion. These functionally mature HILOs contain endocrine-like cell types that, upon transplantation, rapidly re-establish glucose homeostasis in diabetic NOD/SCID mice. Overexpression of the immune checkpoint protein programmed death-ligand 1 (PD-L1) protected HILO xenografts such that they were able to restore glucose homeostasis in immune-competent diabetic mice for 50 days. Furthermore, ex vivo stimulation with interferon-γ induced endogenous PD-L1 expression and restricted T cell activation and graft rejection. The generation of glucose-responsive islet-like organoids that are able to avoid immune detection provides a promising alternative to cadaveric and device-dependent therapies in the treatment of diabetes.
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“This PD-L1 strategy was pushed even further by directly overexpressing PD-L1 in islet-like organoids made from hiPSCs using a lentiviral system.67 These engineered cells were found to evade the immune system in both immune-competent mice and in a humanized mouse model.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [67]
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Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
Trapnell, C., Cacchiarelli, D., Grimsby, J., Pokharel, P., Li, S., Morse, M., Lennon, N. J., Livak, K. J., Mikkelsen, T. S., & Rinn, J. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2859 · Cited by 7,314
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110
Differential analysis of gene regulation at transcript resolution with RNA-seq
Trapnell, C., Hendrickson, D. G., Sauvageau, M., Goff, L., Rinn, J. L., & Pachter, L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2450 · Cited by 3,492
ATAC-seq: a method for assaying chromatin accessibility genome-wide
Buenrostro, J. D., Wu, B., Chang, H. Y., & Greenleaf, W. J. (2015) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb2129s109 · Cited by 3,289
Vascularized and functional human liver from an iPSC-derived organ bud transplant
Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., Zhang, R.-R., Ueno, Y., Zheng, Y.-W., Koike, N., et al. (2013) · Nature · doi:10.1038/nature12271 · Cited by 2,170
Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling
Huang, S.-M. A., Mishina, Y., Liu, S.-M., Cheung, A. K., Stegmeier, F., Michaud, G., Charlat, O., Wiellette, E., Zhang, Y., Wiessner, S., et al. (2009) · Nature · doi:10.1038/nature08356 · Cited by 2,077
Generation of Functional Human Pancreatic β Cells In Vitro
Pagliuca, F. W., Millman, J. R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J. H., Peterson, Q. P., Greiner, D., & Melton, D. A. (2014) · Cell · doi:10.1016/j.cell.2014.09.040 · Cited by 2,025
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Brassard, J. A., Sidharthan, D. S., Orimi, H. E., Ling, S. D., Vdovenko, D., Rioux, Y., Wang, H., Campeau, M.-A., Champion, K. S., Lemaire, F., et al. (2026) · Cell Biomaterials · doi:10.1016/j.celbio.2026.100455 · Cited by 5
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Wang, Y., Nozhat, Z., Duan, T., Chen, S., Ni, Y., Wang, Y., Shen, C., & You, M. (2026) · Cancer Biome and Targeted Therapy · doi:10.66505/cbtt.v1i2.37
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Ye, C., Jin, Z., & Hu, S. S. (2026) · Diabetes Obesity and Metabolism · doi:10.1111/dom.71210
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Mi, C., Xie, C., Tang, J., Gao, Y., Zhang, J., Yang, Y., Tan, G., Zheng, C., & Liu, H. (2026) · Cell Transplantation · doi:10.1177/09636897261486242
Deng, B., Huang, P., Wang, Q., He, Y., Gong, L., Chen, C., Wu, Y., Lu, Z., & Liang, Z. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01825-w
Jalali, P., Wu, A. Y., Alkhazna, S., Celaj, S., & Saeed, A. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105591
Hirani, K., Blaschke, C., Olloqui, C., & Mittal, R. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1915502
van der Walle, C. F. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45791-3.00006-8
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Winstead, C. J., Hodel, M., & Tse, H. M. (2026) · Immunological Reviews · doi:10.1111/imr.70182
Al-issawi, M. M., Gabr, M. M., Khater, S. M., & Abdel-Aziz, A.-A. (2025) · Reports of Biochemistry and Molecular Biology · doi:10.66224/rbmb.14.2.155
Metadata
- Authors
- Yoshihara, E., O’Connor, C., Gasser, E., Wei, Z., Oh, T. G., Tseng, T. W., Wang, D., Cayabyab, F., Dai, Y., Yu, R. T., Liddle, C., Atkins, A. R., Downes, M., & Evans, R. M.
- Affiliations
- Salk Institute for Biological Studies (US)
- The University of Sydney (AU)
- Corresponding author
- Evans, Ronald M.
- ORCID
- Venue
- Nature
- Published
- 2020-08-19
- Volume
- 586
- Issue
- 7830
- Pages
- 606-611
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7872080
- OpenAlex
- W3068518905
- Cited by
- 333
- References
- 44
- Citations by year
- 2026: 28 · 2025: 63 · 2024: 64 · 2023: 46 · 2022: 71 · 2021: 53 · 2020: 8
- FWCI
- 40.67
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-01-19)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (1s10od023689-01a1)
- National Cancer Institute (P30CA014195)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK120480, K01DK120808, P30DK063491)
- National Institute of Environmental Health Sciences (P42ES010337)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 1 diabetes, induced pluripotent stem cells, glucose-stimulated insulin secretion, PD-L1, immune evasion, islet transplantation, graft rejection, interferon-gamma, T cell activation, glucose homeostasis, NOD/SCID mice
- MeSH terms
- Insulin Secretion, Animals, Cell Line, Diabetes Mellitus, Experimental, Female, Glucose, Graft Rejection, Homeostasis, Humans, Immune Tolerance, Islets of Langerhans, Lymphocyte Activation, Male, Organoids, T-Lymphocytes, Islets of Langerhans Transplantation, Mice, SCID, Mice, Inbred NOD, Epigenesis, Genetic, Mice, Immune Evasion, Wnt Signaling Pathway, Wnt4 Protein, B7-H1 Antigen, Heterografts
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