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- Title
Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats.
- Authors
Paez-Mayorga, Jesus; Campa-Carranza, Jocelyn Nikita; Capuani, Simone; Hernandez, Nathanael; Liu, Hsuan-Chen; Chua, Corrine Ying Xuan; Pons-Faudoa, Fernanda Paola; Malgir, Gulsah; Alvarez, Bella; Niles, Jean A.; Argueta, Lissenya B.; Shelton, Kathryn A.; Kezar, Sarah; Nehete, Pramod N.; Berman, Dora M.; Willman, Melissa A.; Li, Xian C.; Ricordi, Camillo; Nichols, Joan E.; Gaber, A. Osama
- Abstract
Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device, which integrates direct vascularization for facile mass transfer and localized immunosuppressant delivery for islet rejection prophylaxis. Here, we investigated NICHE efficacy for allogeneic islet transplantation and long-term diabetes reversal in an immunocompetent, male rat model. We demonstrated that allogeneic islets transplanted within pre-vascularized NICHE were engrafted, revascularized, and functional, reverting diabetes in rats for over 150 days. Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression. Moreover, for translatability efforts, we showed NICHE biocompatibility and feasibility of deployment as well as short-term allogeneic islet engraftment in an MHC-mismatched nonhuman primate model. In sum, the NICHE holds promise as a viable approach for safe and effective islet transplantation and long-term T1D management. Islet transplantation for type 1 diabetes management is hindered by the life-long need for immunosuppressive medications. Here, the authors report an islet encapsulation device with local anti-rejection drug release that achieves long-term diabetes reversal in male rats and reduces drug-related toxicity.
- Subjects
TYPE 1 diabetes; ISLANDS; IMMUNOSUPPRESSION; MALE models; ISLANDS of Langerhans; MASS transfer; RATS
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35629-z