ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Pancreatic islets engineered with SA-FasL protein establish robust localized tolerance by inducing regulatory T cells in mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 78 citations in OpenAlex.
- Advancing Type 1 Diabetes Treatment: 3 PM-Oriented Innovations in Islet Transplantation and Biomaterial Engineering.Diabetes/metabolism research and reviews · 2026Review
- Islets co-engineered with thrombomodulin and CD47 achieve sustained survival in allogeneic recipients without chronic immunosuppression.JCI insight · 2026Article
- Immune modulation for β-cell replacement in type 1 diabetes.Frontiers in immunology · 2026Review
- Affinity-based controlled release of interleukin-4 from scaffolds via biotin-streptavidin interactions for immunomodulation.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Islet Cell Replacement and Regeneration for Type 1 Diabetes: Current Developments and Future Prospects.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Unlocking Transplant Tolerance with Biomaterials.Advanced healthcare materials · 2025Review
- Immune-evasive beta cells in type 1 diabetes: innovations in genetic engineering, biomaterials, and computational modeling.Frontiers in immunology · 2025Review
- From Edmonton to Lantidra and beyond: immunoengineering islet transplantation to cure type 1 diabetes.Frontiers in transplantation · 2025Review
- Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Biomaterial-enhanced treg cell immunotherapy: A promising approach for transplant medicine and autoimmune disease treatment.Bioactive materials · 2024Review
- Retinal transplant immunology and advancements.Stem cell reports · 2024Review
- Encapsulation and immune protection for type 1 diabetes cell therapy.Advanced drug delivery reviews · 2024Review
- Engineering donor lymphocytes with Fas ligand protein effectively prevents acute graft-versus-host disease.Blood advances · 2023Article
- Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes.Cell stem cell · 2023Review
- Engineering pancreatic islets with a novel form of thrombomodulin protein to overcome early graft loss triggered by instant blood-mediated inflammatory reaction.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Article
- A hydrogel platform for co-delivery of immunomodulatory proteins for pancreatic islet allografts.Journal of biomedical materials research. Part A · 2022Article
- FasL microgels induce immune acceptance of islet allografts in nonhuman primates.Science advances · 2022Article
- Therapeutic approaches targeting CD95L/CD95 signaling in cancer and autoimmune diseases.Cell death & disease · 2022Review
- The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?Frontiers in endocrinology · 2022Review
- Local delivery strategies to restore immune homeostasis in the context of inflammation.Advanced drug delivery reviews · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Allogeneic islet transplantation is an important therapeutic approach for the treatment of type 1 diabetes. Clinical application of this approach, however, is severely curtailed by allograft rejection primarily initiated by pathogenic effector T cells regardless of chronic use of immunosuppression. Given the role of Fas-mediated signaling in regulating effector T cell responses, we tested if pancreatic islets can be engineered ex vivo to display on their surface an apoptotic form of Fas ligand protein chimeric with streptavidin (SA-FasL) and whether such engineered islets induce tolerance in allogeneic hosts. Islets were modified with biotin following efficient engineering with SA-FasL protein that persisted on the surface of islets for >1 wk in vitro. SA-FasL-engineered islet grafts established euglycemia in chemically diabetic syngeneic mice indefinitely, demonstrating functionality and lack of acute toxicity. Most importantly, the transplantation of SA-FasL-engineered BALB/c islet grafts in conjunction with a short course of rapamycin treatment resulted in robust localized tolerance in 100% of C57BL/6 recipients. Tolerance was initiated and maintained by CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, as their depletion early during tolerance induction or late after established tolerance resulted in prompt graft rejection. Furthermore, Treg cells sorted from graft-draining lymph nodes, but not spleen, of long-term graft recipients prevented the rejection of unmodified allogeneic islets in an adoptive transfer model, further confirming the Treg role in established tolerance. Engineering islets ex vivo in a rapid and efficient manner to display on their surface immunomodulatory proteins represents a novel, safe, and clinically applicable approach with important implications for the treatment of type 1 diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.