Foster, N. C. et al. State of type 1 diabetes management and outcomes from the T1D exchange in 2016–2018. Diabetes Technol. Ther. 21, 66–72 (2019).
Atkinson, M. A., Eisenbarth, G. S. & Michels, A. W. Type 1 diabetes. Lancet 383, 69–82 (2014).
Shapiro, A. M. J. et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N. Engl. J. Med. 343, 230–238 (2000).
Ryan, E. A. et al. Five-year follow-up after clinical islet transplantation. Diabetes 54, 2060–2069 (2005).
Berney, T. et al. A worldwide survey of activities and practices in clinical islet of Langerhans transplantation. Transpl. Int. 35, 10507 (2022).
Stabler, C. L. & Russ, H. A. Regulatory approval of islet transplantation for treatment of type 1 diabetes: implications and what is on the horizon. Mol. Ther. 31, 3107–3108 (2023).
Cnop, M. et al. Longevity of human islet α- and β-cells. Diabetes Obes. Metab. 13, 39–46 (2011).
Carlsson, P.-O. et al. Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus. Am. J. Transplant. 18, 1735–1744 (2018).
Shapiro, A. M. J. et al. Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device. Cell Rep. Med. 2, 100466 (2021).
Basta, G. et al. Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts. Diabetes Care 34, 2406–2409 (2011).
Li, Y. et al. In vitro platform establishes antigen-specific CD8+ T cell cytotoxicity to encapsulated cells via indirect antigen recognition. Biomaterials 256, 120182 (2020).
Jones, K. S., Sefton, M. V. & Gorczynski, R. M. In vivo recognition by the host adaptive immune system of microencapsulated xenogeneic cells. Transplantation 78, 1454–1462 (2004).
Kobayashi, T. et al. Immune mechanisms associated with the rejection of encapsulated neonatal porcine islet xenografts. Xenotransplantation 13, 547–559 (2006).
Duvivier-Kali, V. F., Omer, A., Lopez-Avalos, M. D., O’Neil, J. J. & Weir, G. C. Survival of microencapsulated adult pig islets in mice in spite of an antibody response. Am. J. Transplant. 4, 1991–2000 (2004).
Kharbikar, B. N., Chendke, G. S. & Desai, T. A. Modulating the foreign body response of implants for diabetes treatment. Adv. Drug. Deliv. Rev. 174, 87–113 (2021).
Veiseh, O. et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat. Mater. 14, 643–651 (2015).
Chang, T. M. S. Semipermeable microcapsules. Science 146, 524–525 (1964).
Lim, F. & Sun Anthony, M. Microencapsulated islets as bioartificial endocrine pancreas. Science 210, 908–910 (1980).
Lee, S. J., Lee, J. B., Park, Y.-W. & Lee, D. Y. In Biomimetic Medical Materials: from Nanotechnology to 3D Bioprinting (ed. Noh, I.) 355–374 (Springer Singapore, 2018).
Kizilel, S., Garfinkel, M. & Opara, E. The bioartificial pancreas: progress and challenges. Diabetes Technol. Ther. 7, 968–985 (2005).
Sakata, N. et al. MRI assessment of ischemic liver after intraportal islet transplantation. Transplantation 87, 825–830 (2009).
Chen, C. et al. Improved intraportal islet transplantation outcome by systemic IKK-β inhibition: NF-κB activity in pancreatic islets depends on oxygen availability. Am. J. Transplant. 11, 215–224 (2011).
Olsson, R., Olerud, J., Pettersson, U. & Carlsson, P. O. Increased numbers of low-oxygenated pancreatic islets after intraportal islet transplantation. Diabetes 60, 2350–2353 (2011).
Shapiro, A. M. J., Pokrywczynska, M. & Ricordi, C. Clinical pancreatic islet transplantation. Nat. Rev. Endocrinol. 13, 268–277 (2017).
Qi, M. et al. A recommended laparoscopic procedure for implantation of microcapsules in the peritoneal cavity of non-human primates. J. Surg. Res. 168, e117–e123 (2011).
Bochenek, M. A. et al. Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques. Nat. Biomed. Eng. 2, 810–821 (2018).
Damyar, K., Farahmand, V., Whaley, D., Alexander, M. & Lakey, J. R. T. An overview of current advancements in pancreatic islet transplantation into the omentum. Islets 13, 115–120 (2021).
Berman, D. M. et al. Long-term survival of nonhuman primate islets implanted in an omental pouch on a biodegradable scaffold. Am. J. Transplant. 9, 91–104 (2008).
Carlsson, P.-O., Palm, F., Andersson, A. & Liss, P. Markedly decreased oxygen tension in transplanted rat pancreatic islets irrespective of the implantation site. Diabetes 50, 489–495 (2001).
Cao, R., Avgoustiniatos, E., Papas, K., Vos, P. & Lakey, J. R. T. Mathematical predictions of oxygen availability in micro‐ and macro‐encapsulated human and porcine pancreatic islets. J. Biomed. Mater. Res. B 108, 343–352 (2019).
Korsgren, O. Islet encapsulation: physiological possibilities and limitations. Diabetes 66, 1748–1754 (2017).
Gilla, R. G. Antigen presentation pathways for immunity to islet transplants: relevance to immunoisolation. Ann. NY Acad. Sci. 875, 255–260 (1999).
Gray, D. W. R. An overview of the immune system with specific reference to membrane encapsulation and islet transplantation. Ann. NY Acad. Sci. 944, 226–239 (2001).
Brauker, J., Martinson, L. A., Young, S. K. & Johnson, R. C. Local inflammatory response around diffusion chambers containing xenografts. Transplantation 61, 1671–1677 (1996).
Kumagai-Braesch, M. et al. The TheraCyte™ device protects against islet allograft rejection in immunized hosts. Cell Transpl. 22, 1137–1146 (2013).
Loudovaris, T., Mandel, T. E. & Charlton, B. Cd4+ T cell mediated destruction of xenografts within cell-impermeable membranes in the absence of Cd8+ T cells and B cells. Transplantation 61, 1678–1684 (1996).
Rayat, G. R. et al. The degree of phylogenetic disparity of islet grafts dictates the reliance on indirect CD4 T-cell antigen recognition for rejection. Diabetes 52, 1433–1440 (2003).
Gray, D. W. R. Encapsulated islet cells: the role of direct and indirect presentation and the relevance to xenotransplantation and autoimmune recurrence. Br. Med. Bull. 53, 777–788 (1997).
O’Shea, G. M., Goosen, M. F. A. & Sun, A. M. Prolonged survival of transplanted islets of Langerhans encapsulated in a biocompatible membrane. Biochim. Biophys. Acta 804, 133–136 (1984).
Kollmer, M., Appel, A. A., Somo, S. I. & Brey, E. M. Long-term function of alginate-encapsulated islets. Tissue Eng. B 22, 34–46 (2016).
Ching, S. H., Bansal, N. & Bhandari, B. Alginate gel particles — a review of production techniques and physical properties. Crit. Rev. Food Sci. Nutr. 57, 1133–1152 (2015).
Dhamecha, D., Movsas, R., Sano, U. & Menon, J. U. Applications of alginate microspheres in therapeutics delivery and cell culture: past, present and future. Int. J. Pharm. 569, 118627 (2019).
King, A., Lau, J., Nordin, A., Sandler, S. & Andersson, A. The effect of capsule composition in the reversal of hyperglycemia in diabetic mice transplanted with microencapsulated allogeneic islets. Diabetes Technol. Ther. 5, 653–663 (2003).
Clayton, H. A., London, N. J. M., Colloby, P. S., Bell, P. R. F. & James, R. F. L. The effect of capsule composition on the biocompatibility of alginate-poly-1-lysine capsules. J. Microencapsul. 8, 221–233 (2008).
King, A., Sandler, S. & Andersson, A. The effect of host factors and capsule composition on the cellular overgrowth on implanted alginate capsules. J. Biomed. Mater. Res. 57, 374–383 (2001).
Thu, B. et al. Alginate polycation microcapsules. Biomaterials 17, 1031–1040 (1996).
Strand, B. L. et al. Poly-l-lysine induces fibrosis on alginate microcapsules via the induction of cytokines. Cell Transpl. 10, 263–275 (2017).
Sawhney, A. S., Pathak, C. P. & Hubbell, J. A. Modification of islet of Langerhans surfaces with immunoprotective poly(ethylene glycol) coatings via interfacial photopolymerization. Biotechnol. Bioeng. 44, 383–386 (1994).
Cruise, G. M., Hegre, O. D., Scharp, D. S. & Hubbell, J. A. A sensitivity study of the key parameters in the interfacial photopolymerization of poly(ethylene glycol) diacrylate upon porcine islets. Biotechnol. Bioeng. 57, 655–665 (1998).
Scharp, D. W. & Marchetti, P. Encapsulated islets for diabetes therapy: history, current progress, and critical issues requiring solution. Adv. Drug. Del. Rev. 67-–68, 35–73 (2014).
Teramura, Y. & Iwata, H. Bioartificial pancreas: microencapsulation and conformal coating of islet of Langerhans. Adv. Drug. Del. Rev. 62, 827–840 (2010).
Zhi, Z.-L., Liu, B., Jones, P. M. & Pickup, J. C. Polysaccharide multilayer nanoencapsulation of insulin-producing β-cells grown as pseudoislets for potential cellular delivery of insulin. Biomacromolecules 11, 610–616 (2010).
Zhi, Z. L., Kerby, A., King, A. J. F., Jones, P. M. & Pickup, J. C. Nano-scale encapsulation enhances allograft survival and function of islets transplanted in a mouse model of diabetes. Diabetologia 55, 1081–1090 (2012).
Bhaiji, T., Zhi, Z.-L. & Pickup, J. C. Improving cellular function and immune protection via layer-by-layer nanocoating of pancreatic islet β-cell spheroids cocultured with mesenchymal stem cells. J. Biomed. Mater. Res. A 100A, 1628–1636 (2012).
Fischer, D., Li, Y., Ahlemeyer, B., Krieglstein, J. & Kissel, T. In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 24, 1121–1131 (2003).
Chanana, M. et al. Interaction of polyelectrolytes and their composites with living cells. Nano Lett. 5, 2605–2612 (2005).
Teramura, Y. & Iwata, H. Cell surface modification with polymers for biomedical studies. Soft Matter. 6, 1081–1091 (2010).
Song, S. & Roy, S. Progress and challenges in macroencapsulation approaches for type 1 diabetes (T1D) treatment: cells, biomaterials, and devices. Biotechnol. Bioeng. 113, 1381–1402 (2016).
Brauker, J. H. et al. Neovascularization of synthetic membranes directed by membrane microarchitecture. J. Biomed. Mater. Res. 29, 1517–1524 (1995).
Faleo, G., Lee, K., Nguyen, V. & Tang, Q. Assessment of immune isolation of allogeneic mouse pancreatic progenitor cells by a macroencapsulation device. Transplantation 100, 1211–1218 (2016).
Agulnick, A. D. et al. Insulin-producing endocrine cells differentiated in vitro from human embryonic stem cells function in macroencapsulation devices in vivo. Stem Cell Transl. Med. 4, 1214–1222 (2015).
Pullen, L. C. Stem cell-derived pancreatic progenitor cells have now been transplanted into patients: report from IPITA 2018. Am. J. Transplant. 18, 1581–1582 (2018).
Henry, R. R. et al. Initial clinical evaluation of VC-01TM combination product — a stem cell-derived islet replacement for type 1 diabetes (T1D). Diabetes 67 (Suppl. 1), 138-OR (2018).
ClinicalTrials.gov A safety, tolerability, and efficacy study of VC-01™ combination product in subjects with type I diabetes mellitus. US National Library of Medicine https://clinicaltrials.gov/ct2/show/results/NCT02239354 (2022).
ClinicalTrials.gov A study to evaluate safety, engraftment, and efficacy of VC-01 in subjects with T1 diabetes mellitus (VC01-103). US National Library of Medicine https://classic.clinicaltrials.gov/ct2/show/NCT04678557 (2019).
Maki, T. et al. Successful treatment of diabetes with the biohybrid artificial pancreas in dogs. Transplantation 51, 43–50 (1991).
Sullivan, S. et al. Biohybrid artificial pancreas: long-term implantation studies in diabetic, pancreatectomized dogs. Science 252, 718–721 (1991).
Maki, T. et al. Treatment of diabetes by xenogeneic islets without immunosuppression: use of a vascularized bioartificial pancreas. Diabetes 45, 342–347 (1996).
Yang, K. et al. A therapeutic convection-enhanced macroencapsulation device for enhancing β cell viability and insulin secretion. Proc. Natl Acad. Sci. USA 118, e2101258118 (2021).
Oppler, S. H. et al. A bioengineered artificial interstitium supports long-term islet xenograft survival in nonhuman primates without immunosuppression. Sci. Adv. 10, eadi4919 (2024).
Hilburger, C. E., Rosenwasser, M. J. & Delcassian, D. The type 1 diabetes immune niche: immunomodulatory biomaterial design considerations for beta cell transplant therapies. J. Immunol. Regen. Med. 17, 100063 (2022).
Gibly, R. F. et al. Advancing islet transplantation: from engraftment to the immune response. Diabetologia 54, 2494–2505 (2011).
Chandorkar, Y., Ravikumar, K. & Basu, B. The foreign body response demystified. ACS Biomater. Sci. Eng. 5, 19–44 (2018).
Mariani, E., Lisignoli, G., Borzì, R. M. & Pulsatelli, L. Biomaterials: foreign bodies or tuners for the immune response? Int. J. Mol. Sci. 20, 636 (2019).
Rafael, E., Wernerson, A., Arner, P., Wu, G. S. & Tibell, A. In vivo evaluation of glucose permeability of an immunoisolation device intended for islet transplantation: a novel application of the microdialysis technique. Cell Transpl. 8, 317–326 (1999).
Matsumoto, S. et al. Clinical porcine islet xenotransplantation under comprehensive regulation. Transplant. Proc. 46, 1992–1995 (2014).
Matsumoto, S., Abalovich, A., Wechsler, C., Wynyard, S. & Elliott, R. B. Clinical benefit of islet xenotransplantation for the treatment of type 1 diabetes. eBioMedicine 12, 255–262 (2016).
Morozov, V. A. et al. No PERV transmission during a clinical trial of pig islet cell transplantation. Virus Res. 227, 34–40 (2017).
Elliott, R. B. et al. Transplantation of micro- and macroencapsulated piglet islets into mice and monkeys. Transplant. Proc. 37, 466–469 (2005).
Elliott, R. B. et al. Intraperitoneal alginate-encapsulated neonatal porcine islets in a placebo-controlled study with 16 diabetic cynomolgus primates. Transplant. Proc. 37, 3505–3508 (2005).
Doloff, J. C. et al. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Nat. Mater. 16, 671–680 (2017).
Dondossola, E. et al. Examination of the foreign body response to biomaterials by nonlinear intravital microscopy. Nat. Biomed. Eng. 1, 0007 (2016).
Vegas, A. J. et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 34, 345–352 (2016).
Vegas, A. J. et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived β cells in immune-competent mice. Nat. Med. 22, 306–311 (2016).
Bose, S. et al. A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells. Nat. Biomed. Eng. 4, 814–826 (2020).
Liu, Q. et al. Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation. Nat. Commun. 10, 5262 (2019).
Liu, W. et al. A safe, fibrosis-mitigating, and scalable encapsulation device supports long-term function of insulin-producing cells. Small 18, e2104899 (2022).
Liu, Q. et al. A zwitterionic polyurethane nanoporous device with low foreign‐body response for islet encapsulation. Adv. Mater. 33, e2102852 (2021).
Chen, T. et al. Alginate encapsulant incorporating CXCL12 supports long-term allo- and xenoislet transplantation without systemic immune suppression. Am. J. Transplant. 15, 618–627 (2015).
Alagpulinsa, D. A. et al. Alginate‐microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression. Am. J. Transplant. 197, 1930–1940 (2019).
Sremac, M. et al. Preliminary studies of the impact of CXCL12 on the foreign body reaction to pancreatic islets microencapsulated in alginate in nonhuman primates. Transplant. Direct 5, e447 (2019).
Su, J., Hu, B.-H., Lowe, W. L., Kaufman, D. B. & Messersmith, P. B. Anti-inflammatory peptide-functionalized hydrogels for insulin-secreting cell encapsulation. Biomaterials 31, 308–314 (2010).
Lin, C.-C., Metters, A. T. & Anseth, K. S. Functional PEG–peptide hydrogels to modulate local inflammation induced by the pro-inflammatory cytokine TNFα. Biomaterials 30, 4907–4914 (2009).
Kuppan, P. et al. Co‐localized immune protection using dexamethasone‐eluting micelles in a murine islet allograft model. Am. J. Transplant. 20, 714–725 (2019).
Bünger, C. M. et al. Deletion of the tissue response against alginate-PLL capsules by temporary release of co-encapsulated steroids. Biomaterials 26, 2353–2360 (2005).
Jiang, K. et al. Local release of dexamethasone from macroporous scaffolds accelerates islet transplant engraftment by promotion of anti-inflammatory M2 macrophages. Biomaterials 114, 71–81 (2017).
Weaver, J. D. et al. Controlled release of dexamethasone from organosilicone constructs for local modulation of inflammation in islet transplantation. Tissue Eng. A 21, 2250–2261 (2015).
Primavera, R. et al. Enhancing islet transplantation using a biocompatible collagen-PDMS bioscaffold enriched with dexamethasone-microplates. Biofabrication 13, 035011 (2021).
Veiseh, O. & Vegas, A. J. Domesticating the foreign body response: recent advances and applications. Adv. Drug. Del. Rev. 144, 148–161 (2019).
Ranta, F. et al. Dexamethasone induces cell death in insulin-secreting cells, an effect reversed by exendin-4. Diabetes 55, 1380–1390 (2006).
Bocca, N. et al. Soft corticosteroids for local immunosuppression: exploring the possibility for the use of loteprednol etabonate for islet transplantation. Pharmazie 63, 226–232 (2008).
Patil, S. D., Papadmitrakopoulos, F. & Burgess, D. J. Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis. J. Control. Rel. 117, 68–79 (2007).
Vaithilingam, V. et al. Co-encapsulation and co-transplantation of mesenchymal stem cells reduces pericapsular fibrosis and improves encapsulated islet survival and function when allografted. Sci. Rep. 7, 10059 (2017).
Jacobson, S., Kumagai-Braesch, M., Tibell, A., Svensson, M. & Flodström-Tullberg, M. Co-transplantation of stromal cells interferes with the rejection of allogeneic islet grafts. Ann. NY Acad. Sci. 1150, 213–216 (2008).
Prud’homme, G. J. Pathobiology of transforming growth factor β in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab. Invest. 87, 1077–1091 (2007).
Ding, Y. et al. Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9. Diabetes 58, 1797–1806 (2009).
Wu, H., Wen, D. & Mahato, R. I. Third-party mesenchymal stem cells improved human islet transplantation in a humanized diabetic mouse model. Mol. Ther. 21, 1778–1786 (2013).
Berman, D. M. et al. Mesenchymal stem cells enhance allogeneic islet engraftment in nonhuman primates. Diabetes 59, 2558–2568 (2010).
Wang, X. et al. Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression. Sci. Adv. 8, eabn0071 (2022).
An, D. et al. Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes. Proc. Natl Acad. Sci. USA 115, E263–E272 (2018).
An, D. et al. An atmosphere‐breathing refillable biphasic device for cell replacement therapy. Adv. Mater. 31, e1905135 (2019).
Ramzy, A. et al. Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes. Cell Stem Cell 28, 2047–2061 e2045 (2021).
Keymeulen, B. et al. Encapsulated stem cell-derived β cells exert glucose control in patients with type 1 diabetes. Nat. Biotechnol. 10.1038/s41587-023-02055-5 (2023).
Pepper, A. R. et al. Diabetes is reversed in a murine model by marginal mass syngeneic islet transplantation using a subcutaneous cell pouch device. Transplantation 99, 2294–2300 (2015).
Bachul, P. et al. 307.5: Modified approach allowed for improved islet allotransplantation into pre-vascularized Sernova Cell Pouch™ device — preliminary results of the phase I/II clinical trial at University of Chicago. Transplantation 105 (12S1), S2 (2021).
Paez-Mayorga, J. et al. Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats. Nat. Commun. 13, 7951 (2022).
Deuse, T. et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat. Biotechnol. 37, 252–258 (2019).
ClinicalTrials.gov An open-label, FIH study evaluating the safety, tolerability, and efficacy of VCTX211 combination product in subjects with T1D. US National Library of Medicine https://classic.clinicaltrials.gov/ct2/show/NCT05565248 (2022).
Reichman, T. W. et al. 836-P: glucose-dependent insulin production and insulin-independence in type 1 diabetes from stem cell-derived, fully differentiated islet cells — updated data from the VX-880 clinical trial. Diabetes 72, 836–83 (2023).
Hogrebe, N. J., Ishahak, M. & Millman, J. R. Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes. Cell Stem Cell 30, 530–548 (2023).
ClinicalTrials.gov A safety, tolerability, and efficacy study of VX-264 in participants with type 1 diabetes. US National Library of Medicine https://classic.clinicaltrials.gov/ct2/show/NCT05791201 (2023).
Cai, E. P. et al. Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes. Nat. Metab. 2, 934–945 (2020).
Lim, D. et al. Engineering designer beta cells with a CRISPR-Cas9 conjugation platform. Nat. Commun. 11, 4043 (2020).
Gerace, D. et al. Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance. Cell Rep. Med. 4, 100879 (2023).
Yoshihara, E. et al. Immune-evasive human islet-like organoids ameliorate diabetes. Nature 586, 606–611 (2020).
Davies, B. The technical risks of human gene editing. Hum. Reprod. 34, 2104–2111 (2019).
Safley, S. A. et al. Inhibition of cellular immune responses to encapsulated porcine islet xenografts by simultaneous blockade of two different costimulatory pathways. Transplantation 79, 409–418 (2005).
Cui, H. et al. Long-term metabolic control of autoimmune diabetes in spontaneously diabetic nonobese diabetic mice by nonvascularized microencapsulated adult porcine islets. Transplantation 88, 160–169 (2009).
Lei, J. et al. FasL microgels induce immune acceptance of islet allografts in nonhuman primates. Sci. Adv. 8, eabm9881 (2022).
Headen, D. M. et al. Local immunomodulation Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance. Nat. Mater. 17, 732–739 (2018).
Shrestha, P. et al. Immune checkpoint CD47 molecule engineered islets mitigate instant blood‐mediated inflammatory reaction and show improved engraftment following intraportal transplantation. Am. J. Transplant. 20, 2703–2714 (2020).
Batra, L. et al. Localized immunomodulation with PD-L1 results in sustained survival and function of allogeneic islets without chronic immunosuppression. J. Immunol. 204, 2840–2851 (2020).
Wu, D. C. et al. Ex vivo expanded human regulatory T cells can prolong survival of a human islet allograft in a humanized mouse model. Transplantation 96, 707–716 (2013).
Yi, S. et al. Adoptive transfer with in vitro expanded human regulatory t cells protects against porcine islet xenograft rejection via interleukin-10 in humanized mice. Diabetes 61, 1180–1191 (2012).
Putnam, A. L. et al. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes 58, 652–662 (2009).
Krzystyniak, A., Gołąb, K., Witkowski, P. & Trzonkowski, P. Islet cell transplant and the incorporation of Tregs. Curr. Opin. Organ. Transplant. 19, 610–615 (2014).
Liu, C. et al. B lymphocyte–directed immunotherapy promotes long-term islet allograft survival in nonhuman primates. Nat. Med. 13, 1295–1298 (2007).
Oura, T. et al. Kidney versus islet allograft survival after induction of mixed chimerism with combined donor bone marrow transplantation. Cell Transpl. 25, 1331–1341 (2016).
Singh, A. et al. Long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes. Nat. Commun. 10, 3495 (2019).
Jansson, L. & Carlsson, P. O. Graft vascular function after transplantation of pancreatic islets. Diabetologia 45, 749–763 (2002).
Jansson, L. et al. Pancreatic islet blood flow and its measurement. Upsala J. Med. Sci. 121, 81–95 (2016).
Davalli, A. M. et al. Vulnerability of islets in the immediate posttransplantation period: dynamic changes in structure and function. Diabetes 45, 1161–1167 (1996).
Bowers, D. T., Song, W., Wang, L. H. & Ma, M. Engineering the vasculature for islet transplantation. Acta Biomater. 95, 131–151 (2019).
De Vos, P. et al. Why do microencapsulated islet grafts fail in the absence of fibrotic overgrowth? Diabetes 48, 1381–1388 (1999).
Citro, A. et al. Directed self-assembly of a xenogeneic vascularized endocrine pancreas for type 1 diabetes. Nat. Commun. 14, 878 (2023).
Citro, A. et al. Biofabrication of a vascularized islet organ for type 1 diabetes. Biomaterials 199, 40–51 (2019).
Wassmer, C. H. et al. Bio-engineering of pre-vascularized islet organoids for the treatment of type 1 diabetes. Transpl. Int. 35, 10214 (2021).
Nalbach, L. et al. Improvement of islet transplantation by the fusion of islet cells with functional blood vessels. EMBO Mol. Med. 13, e12616 (2021).
Chao, X. et al. Comparative study of two common in vitro models for the pancreatic islet with MIN6. Tissue Eng. Regen. Med. 20, 127–141 (2023).
Padera, R. F. & Colton, C. K. Time course of membrane microarchitecture-driven neovascularization. Biomaterials 17, 277–284 (1996).
Sörenby, A., Rafael, E., Tibell, A. & Wernerson, A. Improved histological evaluation of vascularity around an immunoisolation device by correlating number of vascular profiles to glucose exchange. Cell Transpl. 13, 713–720 (2017).
rafael, e, wernerson, a, arner, P. & Tibell, A. In vivo studies on insulin permeability of an immunoisolation device intended for islet transplantation using the microdialysis technique. Eur. Surg. Res. 31, 249–258 (1999).
Rafael, E., Gazelius, B., Wu, G. S. & Tibell, A. Longitudinal studies on the microcirculation around the TheraCyte™ immunoisolation device, using the laser Doppler technique. Cell Transpl. 9, 107–113 (2000).
Rafael, E., Wu, G. S., Hultenby, K., Tibell, A. & Wernerson, A. Improved survival of macroencapsulated islets of Langerhans by preimplantation of the immunoisolating device: a morphometric study. Cell Transpl. 12, 407–412 (2003).
Sörenby, A. K. et al. Preimplantation of an immunoprotective device can lower the curative dose of islets to that of free islet transplantation — studies in a rodent model. Transplantation 86, 364–366 (2008).
Magisson, J. et al. Safety and function of a new pre-vascularized bioartificial pancreas in an allogeneic rat model. J. Tissue Eng. 11, 2041731420924818 (2020).
Pepper, A. R. et al. A prevascularized subcutaneous device-less site for islet and cellular transplantation. Nat. Biotechnol. 33, 518–523 (2015).
Levey, R. E. et al. Assessing the effects of VEGF releasing microspheres on the angiogenic and foreign body response to a 3D printed silicone-based macroencapsulation device. Pharmaceutics 13, 2077 (2021).
Weaver, J. D. et al. Design of a vascularized synthetic poly(ethylene glycol) macroencapsulation device for islet transplantation. Biomaterials 172, 54–65 (2018).
Weaver, J. D. et al. Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. Sci. Adv. 3, e1700184 (2017).
Kakkar, A. et al. Current status of stem cell treatment for type I diabetes mellitus. Tissue. Eng. Regen. Med. 15, 699–709 (2018).
Figliuzzi, M. et al. Bone marrow-derived mesenchymal stem cells improve islet graft function in diabetic rats. Transplant. Proc. 41, 1797–1800 (2009).
Ito, T. et al. Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function. Transplantation 89, 1438–1445 (2010).
Rackham, C. L. et al. Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice. Diabetologia 54, 1127–1135 (2011).
Park, K.-S. et al. Trophic molecules derived from human mesenchymal stem cells enhance survival, function, and angiogenesis of isolated islets after transplantation. Transplantation 89, 509–517 (2010).
Rackham, C. L., Dhadda, P. K., Le Lay, A. M., King, A. J. F. & Jones, P. M. Preculturing islets with adipose-derived mesenchymal stromal cells is an effective strategy for improving transplantation efficiency at the clinically preferred intraportal site. Cell Med. 7, 37–47 (2014).
de Souza, B. M. et al. Effect of co-culture of mesenchymal stem/stromal cells with pancreatic islets on viability and function outcomes: a systematic review and meta-analysis. Islets 9, 30–42 (2017).
Rackham, C. L. et al. Pre-culturing islets with mesenchymal stromal cells using a direct contact configuration is beneficial for transplantation outcome in diabetic mice. Cytotherapy 15, 449–459 (2013).
Sakata, N., Chan, N. K., Chrisler, J., Obenaus, A. & Hathout, E. Bone marrow cell cotransplantation with islets improves their vascularization and function. Transplantation 89, 686–693 (2010).
McGuigan, A. P. & Sefton, M. V. Vascularized organoid engineered by modular assembly enables blood perfusion. Proc. Natl Acad. Sci. USA 103, 11461–11466 (2006).
Vlahos, A. E., Cober, N. & Sefton, M. V. Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets. Proc. Natl Acad. Sci. USA 114, 9337–9342 (2017).
Song, W. et al. Engineering transferrable microvascular meshes for subcutaneous islet transplantation. Nat. Commun. 10, 4602 (2019).
Komatsu, H., Kandeel, F. & Mullen, Y. Impact of oxygen on pancreatic islet survival. Pancreas 47, 533–543 (2018).
Carlsson, P. O., Liss, P., Andersson, A. & Jansson, L. Measurements of oxygen tension in native and transplanted rat pancreatic islets. Diabetes 47, 1027–1032 (1998).
Vériter, S., Gianello, P. & Dufrane, D. Bioengineered sites for islet cell transplantation. Curr. Diab. Rep. 13, 745–755 (2013).
Papas, K. K., De Leon, H., Suszynski, T. M. & Johnson, R. C. Oxygenation strategies for encapsulated islet and beta cell transplants. Adv. Drug. Del. Rev. 139, 139–156 (2019).
Rodriguez-Brotons, A. et al. Impact of pancreatic rat islet density on cell survival during hypoxia. J. Diabetes Res. 2016, 3615286 (2016).
Paredes-Juarez, G. A. et al. DAMP production by human islets under low oxygen and nutrients in the presence or absence of an immunoisolating-capsule and necrostatin-1. Sci. Rep. 5, 14623 (2015).
Ludwig, B. et al. A novel device for islet transplantation providing immune protection and oxygen supply. Horm. Metab. Res. 42, 918–922 (2010).
Neufeld, T. et al. The efficacy of an immunoisolating membrane system for islet xenotransplantation in minipigs. PLoS ONE 8, e70150 (2013).
Ludwig, B. et al. Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes. Proc. Natl Acad. Sci. USA 114, 11745–11750 (2017).
Ludwig, B. et al. Transplantation of human islets without immunosuppression. Proc. Natl Acad. Sci. USA 110, 19054–19058 (2013).
Krishnan, S. R. et al. A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo. Proc. Natl Acad. Sci. USA 120, e2311707120 (2023).
Razavi, M. et al. A collagen based cryogel bioscaffold that generates oxygen for islet transplantation. Adv. Funct. Mater. 30, 1902463 (2020).
Pedraza, E., Coronel, M. M., Fraker, C. A., Ricordi, C. & Stabler, C. L. Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials. Proc. Natl Acad. Sci. USA 109, 4245–4250 (2012).
Coronel, M. M., Geusz, R. & Stabler, C. L. Mitigating hypoxic stress on pancreatic islets via in situ oxygen generating biomaterial. Biomaterials 129, 139–151 (2017).
Liang, J. P. et al. Engineering a macroporous oxygen-generating scaffold for enhancing islet cell transplantation within an extrahepatic site. Acta Biomater. 130, 268–280 (2021).
Wang, L. H. et al. An inverse-breathing encapsulation system for cell delivery. Sci. Adv. 7, eabd5835 (2021).
Wang, L.-H. et al. A bioinspired scaffold for rapid oxygenation of cell encapsulation systems. Nat. Commun. 12, 5846 (2021).
Korsgren, O. et al. Current status of clinical islet transplantation. Transplantation 79, 1289–1293 (2005).
Ricordi, C. & Strom, T. B. Clinical islet transplantation: advances and immunological challenges. Nat. Rev. Immunol. 4, 259–268 (2004).
Owyang, S., Jastrzebska-Perfect, P., Scott, M. & Traverso, G. Re-considering quantity requirements in islet transplantation. Nat. Rev. Bioeng. 1, 382–384 (2023).
Brennan, D. C. et al. Long-term follow-up of the Edmonton protocol of islet transplantation in the United States. Am. J. Transplant. 16, 509–517 (2016).
D’Amour, K. A. et al. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat. Biotechnol. 23, 1534–1541 (2005).
D’Amour, K. A. et al. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat. Biotechnol. 24, 1392–1401 (2006).
Kroon, E. et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat. Biotechnol. 26, 443–452 (2008).
Rezania, A. et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat. Biotechnol. 32, 1121–1133 (2014).
Shapiro, A. M. J. & Verhoeff, K. A spectacular year for islet and stem cell transplantation. Nat. Rev. Endocrinol. 19, 68–69 (2023).
Gala-Lopez, B. L. et al. Subcutaneous clinical islet transplantation in a prevascularized subcutaneous pouch — preliminary experience. CellR4 4, e2132 (2016).
Tang, L., Jennings, T. A. & Eaton, J. W. Mast cells mediate acute inflammatory responses to implanted biomaterials. Proc. Natl Acad. Sci. USA 95, 8841–8846 (1998).
Anderson, J. M., Rodriguez, A. & Chang, D. T. Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2008).
Noskovicova, N., Hinz, B. & Pakshir, P. Implant fibrosis and the underappreciated role of myofibroblasts in the foreign body reaction. Cells 10, 1794 (2021).
Iglesias-Lopez, C., Agusti, A., Obach, M. & Vallano, A. Regulatory framework for advanced therapy medicinal products in Europe and United States. Front. Pharmacol. 10, 921 (2019).
Piemonti, L. et al. US food and drug administration (FDA) panel endorses islet cell treatment for type 1 diabetes: a pyrrhic victory? Transpl. Int. 34, 1182–1186 (2021).
Iglesias-Lopez, C., Obach, M., Vallano, A. & Agusti, A. Comparison of regulatory pathways for the approval of advanced therapies in the European Union and the United States. Cytotherapy 23, 261–274 (2021).
Hering, B. J. et al. Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care 39, 1230–1240 (2016).
Ricordi, C. & Japour, A. Transplanting islet cells can fix brittle diabetes. Why isn’t it available in the U.S.? CellR4 7, e2768 (2019).
Weir, G. C. & Bonner-Weir, S. Why pancreatic islets should be regarded and regulated like organs. CellR4 9, e3083 (2021).
Witkowski, P. et al. The demise of islet allotransplantation in the United States: a call for an urgent regulatory update. Am. J. Transplant. 21, 1365–1375 (2021).
Witkowski, P. et al. Arguments against the requirement of a biological license application for human pancreatic islets: the position statement of the islets for US collaborative presented during the FDA advisory committee meeting. J. Clin. Med. 10, 2878 (2021).
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