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    Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats

    Year: 2022

    Journal: Nat. Commun., Volume 13, DEC 26

    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; Kenyon, Norma S.; Grattoni, Alessandro

    Organizations: Juvenile Diabetes Research Foundation [1-INO-2018-595-A-N]; Vivian L. Smith Foundation; Houston Methodist Research Institute; Diabetes Research Institute; NIH NIDDK [R01DK132104]

    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.
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