The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance
Open accessAbstract
Islet transplantation is a promising therapy for type 1 diabetes. However, chronic immunosuppression to control rejection of allogeneic islets induces morbidities and impairs islet function. T effector cells are responsible for islet allograft rejection and express Fas death receptors following activation, becoming sensitive to Fas-mediated apoptosis. Here, we report that localized immunomodulation using microgels presenting an apoptotic form of the Fas ligand with streptavidin (SA-FasL) results in prolonged survival of allogeneic islet grafts in diabetic mice. A short course of rapamycin treatment boosted the immunomodulatory efficacy of SA-FasL microgels, resulting in acceptance and function of allografts over 200 days. Survivors generated normal systemic responses to donor antigens, implying immune privilege of the graft, and had increased CD4+CD25+FoxP3+ T regulatory cells in the graft and draining lymph nodes. Deletion of T regulatory cells resulted in acute rejection of established islet allografts. This localized immunomodulatory biomaterial-enabled approach may provide an alternative to chronic immunosuppression for clinical islet transplantation.
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“To this end, PD-L1111 or FasL112,113 proteins were immobilized onto the surface of poly(ethylene glycol) microgels, which were then mixed together with allogeneic islets and co-transplanted into either mice111,112 or non-human primates113. In conjunction with a transient rapamycin treatment, these functionalized microgels greatly improved islet survival without the need for long-term immunosuppres”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [112]
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Fas Ligand-Induced Apoptosis as a Mechanism of Immune Privilege
Griffith, T. S., Brunner, T., Fletcher, S. M., Green, D. R., & Ferguson, T. A. (1995) · Science · doi:10.1126/science.270.5239.1189 · Cited by 1,990
International trial of the Edmonton protocol for islet transplantation
Shapiro, A. M. J., Ricordi, C., Hering, B. J., Auchincloss, H., Lindblad, R., Robertson, R. P., Secchi, A., Brendel, M. D., Berney, T., Brennan, D. C., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061267 · Cited by 1,942
Lethal effect of the anti-Fas antibody in mice
Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., & Nagata, S. (1993) · Nature · doi:10.1038/364806a0 · Cited by 1,881
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
Kim, J. M., Rasmussen, J. P., & Rudensky, A. Y. (2006) · Nature Immunology · doi:10.1038/ni1428 · Cited by 1,827
Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation
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mTOR regulates memory CD8 T-cell differentiation
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Brunner, T., Mogil, R. J., LaFace, D., Yoo, N. J., Mahboubi, A., Echeverri, F., Martin, S. J., Force, W. R., Lynch, D. H., Ware, C. F., et al. (1995) · Nature · doi:10.1038/373441a0 · Cited by 1,314
Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells.
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Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease
Lahl, K., Loddenkemper, C., Drouin, C. E., Freyer, J., Arnason, J. E., Eberl, G., Hamann, A., Wagner, H., Huehn, J., & Sparwasser, T. D. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061852 · Cited by 951
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Hydrogel microparticles for biomedical applications
Daly, A. C., Riley, L., Segura, T., & Burdick, J. A. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0148-6 · Cited by 1,285
Zhang, K., Feng, Q., Fang, Z., Gu, L., & Bian, L. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00071 · Cited by 401
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
Anisotropic Rod‐Shaped Particles Influence Injectable Granular Hydrogel Properties and Cell Invasion
Qazi, T. H., Wu, J., Muir, V. G., Weintraub, S., Gullbrand, S. E., Lee, D., Issadore, D., & Burdick, J. A. (2021) · Advanced Materials · doi:10.1002/adma.202109194 · Cited by 181
Hydrogels in Emerging Technologies for Type 1 Diabetes
Fuchs, S., Ernst, A. U., Wang, L., Shariati, K., Wang, X., Liu, Q., & Ma, M. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01062 · Cited by 162
Metadata
- Authors
- Headen, D. M., Woodward, K. B., Coronel, M. M., Shrestha, P., Weaver, J. D., Zhao, H., Tan, M., Hunckler, M. D., Bowen, W. S., Johnson, C. T., Shea, L., Yolcu, E. S., García, A. J., & Shirwan, H.
- Affiliations
- Georgia Institute of Technology (US)
- University of Louisville (US)
- Corresponding author
- Shirwan, Haval
- ORCID
- Venue
- Nature Materials
- Published
- 2018-06-04
- Volume
- 17
- Issue
- 8
- Pages
- 732-739
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- PMC
- PMC6060019
- OpenAlex
- W2807344337
- Cited by
- 175
- References
- 44
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 29 · 2023: 27 · 2022: 24 · 2021: 25 · 2020: 16 · 2019: 23 · 2018: 7
- FWCI
- 18.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Materials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (4t90dk097787-05, 1s10od016264-01a1)
- National Institute of General Medical Sciences (T32GM008169)
- National Institute of Allergy and Infectious Diseases (R21AI113348, U01AI132817, R56AI121281)
- National Institute of Diabetes and Digestive and Kidney Diseases (T90-DK097787, P30DK020572)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (F30AR069472)
- National Institute of Biomedical Imaging and Bioengineering (R21EB020107)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- islet transplantation, type 1 diabetes, allograft rejection, Fas ligand, microgels, streptavidin, rapamycin, regulatory T cells, effector T cells, immune privilege, biomaterials, graft acceptance
- MeSH terms
- Animals, Biocompatible Materials, Transplantation, Homologous, Islets of Langerhans Transplantation, Streptavidin, Mice, Fas Ligand Protein, Immunomodulation
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