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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Islet-like organoids made from hiPSCs directly overexpressing PD-L1 using a lentiviral system were found to evade the immune system in both immune-competent mice and in a humanized mouse model.
“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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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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Recovering Gene Interactions from Single-Cell Data Using Data Diffusion
van Dijk, D., Sharma, R., Nainys, J., Yim, K., Kathail, P., Carr, A. J., Burdziak, C., Moon, K. R., Chaffer, C. L., Pattabiraman, D., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.061 · Cited by 1,829 · see citing works
GOplot: an R package for visually combining expression data with functional analysis
Walter, W., Sánchez‐Cabo, F., & Ricote, M. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv300 · Cited by 1,760 · see citing works
Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
Rezania, A., Bruin, J. E., Arora, P., Rubin, A., Batushansky, I., Asadi, A., O'Dwyer, S., Quiskamp, N., Mojibian, M., Albrecht, T., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.3033 · Cited by 1,575 · see citing works
Tissue expression of PD-L1 mediates peripheral T cell tolerance
Keir, M., Liang, S. C., Guleria, I., Latchman, Y., Qipo, A., Albacker, L., Koulmanda, M., Freeman, G., Sayegh, M., & Sharpe, A. (2006) · Journal of Experimental Medicine · doi:10.1084/jem.20051776 · Cited by 1,264 · see citing works
Identification of novel transcripts in annotated genomes using RNA-Seq
Roberts, A., Pimentel, H., Trapnell, C., & Pachter, L. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr355 · Cited by 963 · see citing works
A choice of death - the signal-transduction of immune-mediated beta-cell apoptosis
Eizirik, D. L., & Mandrup-Poulsen, T. R. (2001) · Diabetologia · doi:10.1007/s001250100021 · Cited by 880 · see citing works
The Programmed Death-1 (PD-1) Pathway Regulates Autoimmune Diabetes in Nonobese Diabetic (NOD) Mice
Ansari, M. J., Salama, A. D., Chitnis, T., Smith, R. N., Yagita∥, H., Akiba, H., Yamazaki, T., Azuma, M., Iwai, H., Khoury, S. J., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022125 · Cited by 806 · see citing works
Controlled induction of human pancreatic progenitors produces functional beta‐like cells in vitro
Russ, H. A., Parent, A. V., Ringler, J. J., Hennings, T. G., Nair, G. G., Shveygert, M., Guo, T., Puri, S., Haataja, L., Cirulli, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201591058 · Cited by 591 · see citing works
Metabolic Signaling in Fuel-Induced Insulin Secretion
Prentki, M., Matschinsky, F. M., & Madiraju, S. R. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.018 · Cited by 548 · see citing works
Nair, G. G., Liu, J. S., Russ, H. A., Tran, S., Saxton, M. S., Chen, R., Juang, C., Li, M.-L., Nguyen, V. Q., Giacometti, S., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0271-4 · Cited by 472 · see citing works
Extracting Biological Meaning from Large Gene Lists with DAVID
Huang, D. W., Sherman, B. T., Zheng, X. M., Yang, J., Imamichi, T., Stephens, R. M., & Lempicki, R. A. (2009) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1311s27 · Cited by 457 · see citing works
Zhou, Q., & Melton, D. A. (2018) · Nature · doi:10.1038/s41586-018-0088-0 · Cited by 384 · see citing works
Blum, B., Hrvatin, S., Schuetz, C., Bonal, C., Rezania, A., & Melton, D. (2012) · Nature Biotechnology · doi:10.1038/nbt.2141 · Cited by 349 · see citing works
Identification of proliferative and mature β-cells in the islets of Langerhans
Bader, E., Migliorini, A., Gegg, M., Moruzzi, N., Gerdes, J. M., Roscioni, S. S., Bakhti, M., Brandl, E., Irmler, M., Beckers, J., et al. (2016) · Nature · doi:10.1038/nature18624 · Cited by 338 · see citing works
Differentiated human stem cells resemble fetal, not adult, β cells
Hrvatin, S., O’Donnell, C. W., Deng, F., Millman, J. R., Pagliuca, F. W., DiIorio, P., Rezania, A., Gifford, D. K., & Melton, D. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400709111 · Cited by 302 · see citing works
Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion
van der Meulen, T., Donaldson, C. J., Cáceres, E., Hunter, A. E., Cowing-Zitron, C., Pound, L. D., Adams, M. W., Zembrzycki, A., Grove, K. L., & Huising, M. O. (2015) · Nature Medicine · doi:10.1038/nm.3872 · Cited by 256 · see citing works
Toward the development of a global induced pluripotent stem cell library
Turner, M., Leslie, S., Martin, N. G., Peschanski, M., Rao, M., Taylor, C. J., Trounson, A., Turner, D., Yamanaka, S., & Wilmut, I. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.08.003 · Cited by 245 · see citing works
MHC matching improves engraftment of iPSC-derived neurons in non-human primates
Morizane, A., Kikuchi, T., Hayashi, T., Mizuma, H., Takara, S., Doi, H., Mawatari, A., Glasser, M. F., Shiina, T., Ishigaki, H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00926-5 · Cited by 244 · see citing works
Stem cell therapies for treating diabetes: progress and remaining challenges
Sneddon, J. B., Tang, Q., Stock, P., Bluestone, J., Roy, S., Desai, T., & Hebrok, M. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.05.016 · Cited by 222 · see citing works
Rui, J., Deng, S., Arazi, A., Perdigoto, A. L., Liu, Z. Z., & Herold, K. C. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.01.005 · Cited by 207 · see citing works
Vitamin D Switches BAF Complexes to Protect β Cells
Wei, Z., Yoshihara, E., He, N., Hah, N., Fan, W., Pinto, A. F. M., Huddy, T. F., Wang, Y., Ross, B., Estepa, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.04.013 · Cited by 206 · see citing works
Self-citationColli, M. L., Hill, J. L. E., Marroquí, L., Hopkinson, J. R., dos Santos, R. S., Leete, P., de Brachène, A. C., de Paula, F. M. M., Beeck, A. O. D., Castela, Â., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.09.040 · Cited by 193 · see citing works
Yoshihara, E., Wei, Z., Lin, C.-S., Fang, S., Ahmadian, M., Kida, Y. S., Tseng, T. W., Dai, Y., Yu, R. T., Liddle, C., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.005 · Cited by 165 · see citing works
Self-citationOsum, K. C., Burrack, A. L., Martinov, T., Sahli, N. L., Mitchell, J. S., Tucker, C., Pauken, K. E., Papas, K. K., Balamurugan, A. N., Spanier, J. A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-26471-9 · Cited by 147 · see citing works
Paracrine signals regulate human liver organoid maturation from iPSC
Asai, A., Aihara, E., Watson, C. L., Mourya, R., Mizuochi, T., Shivakumar, P., Phelan, K. J., Mayhew, C. N., Helmrath, M. A., Takebe, T., et al. (2017) · Development · doi:10.1242/dev.142794 · Cited by 128 · see citing works
Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity
Yoshihara, E., Fujimoto, S., Inagaki, N., Okawa, K., Masaki, S., Yodoi, J., & Masutani, H. (2010) · Nature Communications · doi:10.1038/ncomms1127 · Cited by 117 · see citing works
Self-citationTGFβ-dependent expression of PD-1 and PD-L1 controls CD8+ T cell anergy in transplant tolerance
Baas, M. C., Besançon, A., Goncalves, T., Valette, F., Yagita∥, H., Sawitzki, B., Volk, H., Waeckel-Énée, E., Rocha, B., Chatenoud, L., et al. (2016) · eLife · doi:10.7554/elife.08133 · Cited by 116 · see citing works
van der Meulen, T., Xie, R., Kelly, O. G., Vale, W., Sander, M., & Huising, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052181 · Cited by 98 · see citing works
Protective Role of Programmed Death 1 Ligand 1 (PD-L1)in Nonobese Diabetic Mice
Wang, C.-J., Chou, F., Chu, C.-H., Wu, J., Lin, S., Chang, D., & Sytwu, H. (2008) · Diabetes · doi:10.2337/db07-1260 · Cited by 88 · see citing works
All mixed up: defining roles for β-cell subtypes in mature isletsPreprint
Liu, J. S. E., & Hebrok, M. (2017) · Genes & Development · doi:10.1101/gad.294389.116 · Cited by 68 · see citing works
Closing in on Mass Production of Mature Human Beta Cells.
Kieffer, T. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.05.014 · Cited by 40 · see citing works
PD-1 pathway-mediated regulation of islet-specific CD4+ T cell subsets in autoimmune diabetes
Martinov, T., Spanier, J. A., Pauken, K. E., & Fife, B. T. (2016) · Immunoendocrinology · doi:10.14800/ie.1164 · Cited by 24 · see citing works
PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice
Ma, D., Duan, W., Li, Y., Wang, Z., Li, S., Gong, N., Chen, G., Chen, Z., Wan, C., & Yang, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0152087 · Cited by 20 · see citing works
Flagged first, then by citations
1 of the 44 references couldn’t be matched to a known paper.
Cited by
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Zhao, Z., Chen, X., Dowbaj, A. M., Sljukic, A., Bratlie, K., Lin, L., Fong, E. L. S., Balachander, G. M., Chen, Z., Soragni, A., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00174-y · Cited by 1,001 · see citing works
Engineering the next generation of cell-based therapeutics
Bashor, C. J., Hilton, I. B., Bandukwala, H. S., Smith, D. M., & Omid Veiseh, A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00476-6 · Cited by 448 · see citing works
Balboa, D., Barsby, T., Lithovius, V., Saarimäki-Vire, J., Omar-Hmeadi, M., Dyachok, O., Montaser, H., Lund, P.-E., Yang, M., Ibrahim, H., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01219-z · Cited by 433 · see citing works
Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids
Marsee, A., Roos, F. J. M., Verstegen, M. M. A., Marsee, A., Roos, F., Verstegen, M., Clevers, H., Vallier, L., Takebe, T., Huch, M., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.04.005 · Cited by 310 · see citing works
Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models
Urzì, O., Gasparro, R., Costanzo, E., Luca, A. D., Giavaresi, G., Fontana, S., & Alessandro, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512046 · Cited by 247 · see citing works
Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes
Hogrebe, N. J., Ishahak, M., & Millman, J. R. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.04.002 · Cited by 210 · see citing works
Integrating organoids and organ-on-a-chip devices
Zhao, Y., Landau, S., Okhovatian, S., Liu, C., Lu, R. X. Z., Lai, B. F. L., Wu, Q., Kieda, J., Cheung, K., Rajasekar, S., et al. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00207-z · Cited by 206 · see citing works
Immunological considerations and challenges for regenerative cellular therapies
Petrus-Reurer, S., Romano, M., Howlett, S., Jones, J., Lombardi, G., & Saeb‐Parsy, K. (2021) · Communications Biology · doi:10.1038/s42003-021-02237-4 · Cited by 160 · see citing works
Single-cell transcriptomic and spatial landscapes of the developing human pancreas
Olaniru, O. E., Kadolsky, U. D., Kannambath, S., Vaikkinen, H., Fung, K., Dhami, P., & Persaud, S. J. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.11.009 · Cited by 138 · see citing works
Organoid based personalized medicine: from bench to bedside
Li, Y., Tang, P., Cai, S., Peng, J., & Hua, G. (2020) · Cell Regeneration · doi:10.1186/s13619-020-00059-z · Cited by 138 · see citing works
Applications of iPSC-derived beta cells from patients with diabetes
Maxwell, K. G., & Millman, J. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100238 · Cited by 118 · see citing works
Engineering islets from stem cells for advanced therapies of diabetes
Siehler, J., Blöchinger, A. K., Meier, M., & Lickert, H. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00262-w · Cited by 125 · see citing works
Advances in Pancreatic Islet Transplantation Sites for the Treatment of Diabetes
Cayabyab, F., Nih, L. R., & Yoshihara, E. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.732431 · Cited by 119 · see citing works
Self-citationPartners in Crime: Beta-Cells and Autoimmune Responses Complicit in Type 1 Diabetes Pathogenesis
Toren, E., Burnette, K., Banerjee, R. R., Hunter, C. S., & Tse, H. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.756548 · Cited by 110 · see citing works
Hu, X., Gattis, C., Olroyd, A. G., Friera, A. M., White, K. A., Young, C., Basco, R., Lamba, M., Wells, F., Ankala, R., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adg5794 · Cited by 104 · see citing works
How the mechanical microenvironment of stem cell growth affects their differentiation: a review
Zhang, X., Zhang, S., & Wang, T. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-03070-0 · Cited by 100 · see citing works
The promise of stem cell-derived islet replacement therapy
Melton, D. (2021) · Diabetologia · doi:10.1007/s00125-020-05367-2 · Cited by 96 · see citing works
TXNIP/TBP-2: A Master Regulator for Glucose Homeostasis
Yoshihara, E. (2020) · Antioxidants · doi:10.3390/antiox9080765 · Cited by 96 · see citing works
Self-citationParent, A. V., Faleo, G., Chavez, J., Saxton, M., Berrios, D. I., Kerper, N. R., Tang, Q., & Hebrok, M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109538 · Cited by 96 · see citing works
Yao, Q., Cheng, S., Pan, Q., Yu, J., Cao, G., Li, L., & Cao, H. (2024) · MedComm · doi:10.1002/mco2.735 · Cited by 97 · see citing works
Landscape of human organoids: Ideal model in clinics and research
Han, X., Cai, C., Deng, W., Shi, Y., Li, L., Wang, C., Zhang, J., Rong, M., Liu, J., Fang, B., et al. (2024) · The Innovation · doi:10.1016/j.xinn.2024.100620 · Cited by 98 · see citing works
Grattoni, A., Korbutt, G., Tomei, A. A., García, A. J., Pepper, A. R., Stabler, C., Brehm, M., Papas, K., Citro, A., Shirwan, H., et al. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01029-0 · Cited by 92 · see citing works
Augsornworawat, P., Hogrebe, N. J., Ishahak, M., Schmidt, M. D., Marquez, E., Maestas, M. M., Veronese-Paniagua, D., Gale, S. E., Miller, J. R., Velazco-Cruz, L., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01150-8 · Cited by 85 · see citing works
Gerace, D., Zhou, Q., Kenty, J. H.-R., Veres, A., Sintov, E., Wang, X., Boulanger, K. R., Li, H., & Melton, D. A. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100879 · Cited by 88 · see citing works
Silva, I. B. B., Kimura, C. H., Colantoni, V. P., & Sogayar, M. (2022) · Stem cell research & therapeutics · doi:10.1186/s13287-022-02977-y · Cited by 68 · see citing works
Roles and action mechanisms of WNT4 in cell differentiation and human diseases: a review
Zhang, Q., Pan, Y., Ji, J., Xu, Y., Zhang, Q., & Qin, L. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00668-w · Cited by 84 · see citing works
The Human Islet: Mini-Organ With Mega-Impact
Walker, J. T., Saunders, D. C., Briššová, M., & Powers, A. C. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab010 · Cited by 80 · see citing works
Advances in Encapsulation and Delivery Strategies for Islet Transplantation
Wu, S., Wang, L., Fang, Y., Huang, H. W., You, X., & Wu, J. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202100965 · Cited by 78 · see citing works
The Wnt Signaling Pathway in Diabetic Nephropathy
Wang, H., Zhang, R., Wu, X., Chen, Y., Ji, W., Wang, J., Zhang, Y., Xia, Y., Tang, Y., & Yuan, J. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.701547 · Cited by 76 · see citing works
Deciphering early human pancreas development at the single-cell level
Ma, Z., Zhang, X., Zhong, W., Yi, H., Chen, X., Zhao, Y., Ma, Y., Song, E., & Xu, T. (2023) · Nature Communications · doi:10.1038/s41467-023-40893-8 · Cited by 73 · see citing works
Gao, X., Cheng, W., Zhang, X., Zhou, Z., Ding, Z., Zhou, X., Lü, Q., & Kaplan, D. L. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c19229 · Cited by 75 · see citing works
Towards a Functional Cure for Diabetes Using Stem Cell-Derived Beta Cells: Are We There Yet?
Bourgeois, S., Sawatani, T., Mulders, A. V., Leu, N. D., Heremans, Y., Heimberg, H., Cnop, M., & Staels, W. (2021) · Cells · doi:10.3390/cells10010191 · Cited by 61 · see citing works
Goswami, D., Domingo‐Lopez, D. A., Ward, N. A., Millman, J. R., Duffy, G. P., Dolan, E. B., & Roche, E. T. (2021) · Advanced Science · doi:10.1002/advs.202100820 · Cited by 68 · see citing works
Maturation of beta cells: lessons from in vivo and in vitro models
Barsby, T., & Otonkoski, T. (2022) · Diabetologia · doi:10.1007/s00125-022-05672-y · Cited by 66 · see citing works
Protecting Stem Cell Derived Pancreatic Beta-Like Cells From Diabetogenic T Cell Recognition
Castro-Gutiérrez, R., Alkanani, A. K., Mathews, C. E., Michels, A. W., & Russ, H. A. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.707881 · Cited by 60 · see citing works
Human pluripotent stem cell-derived insulin-producing cells: A regenerative medicine perspective
Migliorini, A., Nostro, M. C., & Sneddon, J. B. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.03.021 · Cited by 61 · see citing works
The Importance of Proper Oxygenation in 3D Culture
Tse, H., Gardner, G., Domínguez-Bendala, J., & Fraker, C. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.634403 · Cited by 54 · see citing works
Engineering immune-evasive allogeneic cellular immunotherapies
Martin, K. E., Hammer, Q., Perica, K., Sadelain, M., & Malmberg, K. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01022-8 · Cited by 61 · see citing works
Generating 3D human cardiac constructs from pluripotent stem cells
Liu, C., Feng, X., Li, G., Gokulnath, P., & Xiao, J. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.103813 · Cited by 57 · see citing works
Wang, X., Brown, N. K., Wang, B., Shariati, K., Wang, K., Fuchs, S., Melero‐Martin, J. M., & Ma, M. (2021) · Advanced Science · doi:10.1002/advs.202003708 · Cited by 57 · see citing works
Differential Function and Maturation of Human Stem Cell-Derived Islets After Transplantation
Maxwell, K. G., Kim, M. H., Gale, S. E., & Millman, J. R. (2022) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szab013 · Cited by 54 · see citing works
Progress in Organ Bioprinting for Regenerative Medicine
Wang, X. S., Zhang, D., Singh, Y. P., Yeo, M., Deng, G., Lai, J., Chen, F., Ozbolat, I. T., & Yu, Y. (2024) · Engineering · doi:10.1016/j.eng.2024.04.023 · Cited by 59 · see citing works
CD81 marks immature and dedifferentiated pancreatic β-cells
Salinno, C., Büttner, M., Cota, P., Tritschler, S., Tarquis-Medina, M., Bastidas-Ponce, A., Scheibner, K., Burtscher, I., Böttcher, A., Theis, F. J., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101188 · Cited by 52 · see citing works
Transcriptional mechanisms of pancreatic β-cell maturation and functional adaptation
Wortham, M., & Sander, M. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.04.011 · Cited by 56 · see citing works
Human expandable pancreatic progenitor–derived β cells ameliorate diabetes
Ma, X., Lu, Y., Zhou, Z., Li, Q., Chen, X., Wang, W., Jin, Y., Hu, Z., Chen, G., Deng, Q., et al. (2022) · Science Advances · doi:10.1126/sciadv.abk1826 · Cited by 60 · see citing works
Islet organoid as a promising model for diabetes
Zhang, X., Ma, Z., Song, E., & Xu, T. (2021) · Protein & Cell · doi:10.1007/s13238-021-00831-0 · Cited by 52 · see citing works
Wang, X., Wang, K., Yu, M., Velluto, D., Hong, X., Wang, B., Chiu, A., Melero-Martin, J. M., Tomei, A. A., & Ma, M. (2022) · Science Advances · doi:10.1126/sciadv.abn0071 · Cited by 62 · see citing works
Emerging diabetes therapies: Bringing back the β-cells
Basile, G., Qadir, F., Mauvais-Jarvis, F., Vetere, A., Shoba, V., Modell, A. E., Pastori, R., Russ, H., Wagner, B., & Domínguez-Bendala, J. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101477 · Cited by 47 · see citing works
Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction
Jin, H., Xue, Z., Liu, J., Ma, B., Yang, J., & Lei, L. (2024) · Biomaterials Research · doi:10.34133/bmr.0016 · Cited by 53 · see citing works
Stomach-derived human insulin-secreting organoids restore glucose homeostasis
Huang, X., Gu, W. Y., Zhang, J., Lan, Y., Colarusso, J. L., Li, S., Pertl, C., Lü, J., Kim, H., Zhu, J., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01130-y · Cited by 54 · see citing works
From organoids to organoids-on-a-chip: Current applications and challenges in biomedical research
Liu, K., Chen, X., Fan, Z., Ren, F., Liu, J., & Hu, B. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003535 · Cited by 56 · see citing works
Progress and challenges in developing allogeneic cell therapies
Deuse, T., & Schrepfer, S. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.03.004 · Cited by 51 · see citing works
Organoids and regenerative hepatology
Jalan‐Sakrikar, N., Brevini, T., Huebert, R. C., & Sampaziotis, F. (2022) · Hepatology · doi:10.1002/hep.32583 · Cited by 50 · see citing works
Protection of cell therapeutics from antibody-mediated killing by CD64 overexpression
Gravina, A., Tediashvili, G., Rajalingam, R., Quandt, Z., Deisenroth, C., Schrepfer, S., & Deuse, T. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01540-7 · Cited by 48 · see citing works
Current status of stem cell therapy for type 1 diabetes: a critique and a prospective consideration
Ghoneim, M. A., Gabr, M. M., El-Halawani, S. M., & Refaie, A. F. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03636-0 · Cited by 49 · see citing works
Mao, X., Wu, S., Huang, D., & Li, C. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.03.006 · Cited by 51 · see citing works
iPSC-Derived Organoids as Therapeutic Models in Regenerative Medicine and Oncology
Turhan, A. G., Hwang, J. W., Chaker, D., Tasteyre, A., Latsis, T., Griscelli, F., Desterke, C., & Griscelli, A. B. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.728543 · Cited by 46 · see citing works
Emerging immunomodulatory strategies for cell therapeutics
Chua, C. Y. X., Jiang, A. Y., Eufrásio-da-Silva, T., Dolatshahi‐Pirouz, A., Langer, R., Orive, G., & Grattoni, A. (2022) · Trends in biotechnology · doi:10.1016/j.tibtech.2022.11.008 · Cited by 46 · see citing works
Identification of unique cell type responses in pancreatic islets to stress
Maestas, M. M., Ishahak, M., Augsornworawat, P., Veronese-Paniagua, D., Maxwell, K. G., Velazco-Cruz, L., Marquez, E., Sun, J., Shunkarova, M., Gale, S. E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49724-w · Cited by 51 · see citing works
Human Pluripotent Stem Cells to Model Islet Defects in Diabetes
Balboa, D., Iworima, D. G., & Kieffer, T. J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.642152 · Cited by 47 · see citing works
Sintov, E., Nikolskiy, I., Barrera, V., Hyoje-Ryu Kenty, J., Atkin, A. S., Gerace, D., Ho Sui, S. J., Boulanger, K., & Melton, D. A. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.08.002 · Cited by 45 · see citing works
Fantuzzi, F., Toivonen, S., Schiavo, A. A., Chae, H., Mohammad, T., Sawatani, T., Pachera, N., Cai, Y., Vinci, C., Virgilio, E., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.967765 · Cited by 42 · see citing works
Guan, H., Tian, J., Wang, Y., Niu, P., Zhang, Y., Zhang, Y., Fang, X., Miao, R., Yin, R., & Tong, X. (2024) · European journal of medical research · doi:10.1186/s40001-024-01739-1 · Cited by 42 · see citing works
Modeling human T1D-associated autoimmune processes
Maharlooei, M. K., Madley, R., Borsotti, C., Ferreira, L. M. R., Sharp, R. C., Brehm, M. A., Greiner, D. L., Parent, A. V., Anderson, M. S., Sykes, M., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101417 · Cited by 42 · see citing works
Jiang, L., Shen, Y., Liu, Y., Zhang, L. J., & Jiang, W. (2022) · Theranostics · doi:10.7150/thno.66670 · Cited by 42 · see citing works
Genetically engineered hypoimmunogenic cell therapy
Hotta, A., Schrepfer, S., & Nagy, A. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00219-9 · Cited by 41 · see citing works
Immune Protection of Stem Cell-Derived Islet Cell Therapy for Treating Diabetes
Tahbaz, M., & Yoshihara, E. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.716625 · Cited by 42 · see citing works
Self-citationType 1 diabetes and engineering enhanced islet transplantation
Jeyagaran, A., Lu, C., Zbinden, A., Birkenfeld, A. L., Brucker, S. Y., & Layland, S. L. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114481 · Cited by 41 · see citing works
Piñeros, A. R., Kulkarni, A., Gao, H., Orr, K. S., Glenn, L. M., Huang, F., Liu, Y., GANNON, M. A., Syed, F., Wu, W., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111011 · Cited by 38 · see citing works
Organoid-guided precision hepatology for metabolic liver disease
Osonoi, S., & Takebe, T. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.01.002 · Cited by 40 · see citing works
Immune Editing: Overcoming Immune Barriers in Stem Cell Transplantation
Meissner, T. B., Schulze, H. S., & Dale, S. M. (2022) · Current Stem Cell Reports · doi:10.1007/s40778-022-00221-0 · Cited by 39 · see citing works
NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development
Bohuslavová, R., Fabriciova, V., Smolík, O., Lebrón‐Mora, L., Abaffy, P., Benesova, S., Žucha, D., Valihrach, L., Berková, Z., Saudek, F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41306-6 · Cited by 39 · see citing works
A Century-long Journey From the Discovery of Insulin to the Implantation of Stem Cell–derived Islets
Ramzy, A., Belmonte, P. J., Braam, M. J. S., Ida, S., Wilts, E. M., Levings, M. K., Rezania, A., & Kieffer, T. J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac021 · Cited by 36 · see citing works
Encapsulated islet transplantation
Liu, S. S., Shim, S., Kudo, Y., Stabler, C. L., O’Cearbhaill, E. D., Karp, J. M., & Yang, K. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00238-6 · Cited by 41 · see citing works
Genetic Engineering of Immune Evasive Stem Cell-Derived Islets
Sackett, S. D., Kaplan, S. J., Mitchell, S. A., Brown, M. E., Burrack, A. L., Grey, S., Huangfu, D., & Odorico, J. (2022) · Transplant International · doi:10.3389/ti.2022.10817 · Cited by 32 · see citing works
Pancreatic β-cell failure, clinical implications, and therapeutic strategies in type 2 diabetes
Cui, D., Feng, X., Lei, S., Zhang, H., Hu, W., Yang, S., Yu, X., & Su, Z. (2024) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003034 · Cited by 36 · see citing works
Jun, Y., Nguyen-Ngoc, K.-V., Sai, S., Bender, R. H. F., Gong, W., Kravets, V. V., Zhu, H., Hatch, C. J., Schlichting, M., Gaetani, R., et al. (2022) · Developmental Cell · doi:10.1016/j.devcel.2025.04.024 · Cited by 43 · see citing works
Cefalu, W. T., Andersen, D. K., Arreaza-Rubín, G., Pin, C. L., Sato, S. M., Verchere, C. B., Woo, M., & Rosenblum, N. D. (2021) · Diabetes Care · doi:10.2337/dci21-0051 · Cited by 36 · see citing works
From Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes
den Hollander, N. H. M., & Roep, B. O. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.932086 · Cited by 32 · see citing works
Feng, L., Chao, J.-F., Ye, P., Luong, Q., Sun, G.-Q., Liu, W., Cui, Q., Flores, S., Jackson, N., Shayento, A. N. H., et al. (2023) · Advancement of science · doi:10.1002/advs.202206910 · Cited by 32 · see citing works
An in situ dual-anchoring strategy for enhanced immobilization of PD-L1 to treat autoimmune diseases
Wang, S., Zhang, Y., Wang, Y., Yang, Y., Zhao, S., Sheng, T., Zhang, Y., Gu, Z., Wang, J., & Yu, J. (2023) · Nature Communications · doi:10.1038/s41467-023-42725-1 · Cited by 32 · see citing works
Tondin, A. R., & Lanzoni, G. (2025) · BioDrugs · doi:10.1007/s40259-025-00703-7 · Cited by 32 · see citing works
Ho, B. X., Teo, A. K. K., & Ng, N. H. J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1375177 · Cited by 32 · see citing works
Zhu, D., Chen, Z.-X., Guo, K., Xie, Q., Zou, Y., Mou, Q.-Z., Zhou, Z.-J., & Jin, G.-X. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.02.001 · Cited by 30 · see citing works
From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Immunological Considerations
Refaie, A. F., Elbassiouny, B. L., Kloc, M., Sabek, O. M., Khater, S. M., Ismail, A. M., Mohamed, R. H., & Ghoneim, M. A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.690623 · Cited by 31 · see citing works
Gravina, A., Tediashvili, G., Zheng, Y., Iwabuchi, K. A., Peyrot, S. M., Roodsari, S. Z., Gargiulo, L., Kaneko, S., Osawa, M., Schrepfer, S., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.10.003 · Cited by 30 · see citing works
Yang, Z., Zhang, Z., Li, L., Jing, Z., Ma, Y., Lan, T., Li, Y., Lin, Z., Fang, W., Zhang, J., et al. (2024) · Diabetes · doi:10.2337/db23-0987 · Cited by 30 · see citing works
Engineering human pluripotent stem cell lines to evade xenogeneic transplantation barriers
Pizzato, H. A., Alonso‐Guallart, P., Woods, J., Jóhannesson, B., Connelly, J. P., Fehniger, T. A., Atkinson, J. P., Pruett‐Miller, S. M., Monsma, F. J., & Bhattacharya, D. (2024) · Stem Cell Reports · doi:10.1016/j.stemcr.2023.12.003 · Cited by 28 · see citing works
Bioprinting of bespoke islet-specific niches to promote maturation of stem cell-derived islets
Kim, M., Cho, S., Hwang, D. G., Shim, I., Kim, S. C., Jang, J., & Jang, J.-A. (2025) · Nature Communications · doi:10.1038/s41467-025-56665-5 · Cited by 31 · see citing works
Metabolic Studies in Organoids: Current Applications, Opportunities and Challenges
Richiardone, E., den Bossche, V. V., & Corbet, C. (2022) · Organoids · doi:10.3390/organoids1010008 · Cited by 29 · see citing works
Karpov, D. S., Sosnovtseva, A. O., Pylina, S. V., Bastrich, A., Petrova, D. A., Kovalev, M. A., Shuvalova, A. I., Константиновна, Е. А., & Mokrysheva, N. G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417320 · Cited by 29 · see citing works
Immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation
Wang, Y., Huang, R., Lu, Y., Liu, M., & Mo, R. (2024) · Nature Communications · doi:10.1038/s41467-024-49135-x · Cited by 28 · see citing works
Islet Regeneration: Endogenous and Exogenous Approaches
Docherty, F. M., & Sussel, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073306 · Cited by 28 · see citing works
From Pancreatic β-Cell Gene Networks to Novel Therapies for Type 1 Diabetes
Eizirik, D. L., Szymczak, F., Alvelos, M. I., & Martin, F. (2021) · Diabetes · doi:10.2337/dbi20-0046 · Cited by 28 · see citing works
Overcoming the Limitations of Stem Cell-Derived Beta Cells
Karimova, M. V., Gvazava, I. G., & Vorotelyak, E. A. (2022) · Biomolecules · doi:10.3390/biom12060810 · Cited by 30 · see citing works
Zhu, B., Wang, D., Pan, H., Gong, T., Ren, Q., Wang, Z., & Guo, Y. (2022) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2022.113017 · Cited by 28 · see citing works
Self-citationZhu, Z., Cheng, Y., Liu, X., Ding, W., Liu, J., Ling, Z., & Wu, L. (2025) · Cell Transplantation · doi:10.1177/09636897241303271 · Cited by 27 · see citing works
Organoid: Bridging the gap between basic research and clinical practice
Weng, G., Tao, J., Liu, Y., Qiu, J., Su, D., Wang, R., Luo, W., & Zhang, T. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216353 · Cited by 27 · see citing works
Katsumoto, K., Yennek, S., Chen, C., Delgadillo-Silva, L. F., Traikov, S., Sever, D., Azad, A., Shan, J., Vainio, S. J., Ninov, N., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33841-5 · Cited by 25 · see citing works
Ge, J.-Y., Wang, Y., Li, Q., Liu, F.-K., Lei, Q.-K., & Zheng, Y. (2024) · PeerJ · doi:10.7717/peerj.18422 · Cited by 25 · see citing works
- 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 › Surgery › 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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