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

Jesus Paez-Mayorga, Jocelyn Nikita Campa-Carranza, Simone Capuani, Nathanael Hernandez, Hsuan-Chen Liu, Corrine Ying Xuan Chua, Fernanda Paola Pons-Faudoa, Gulsah Malgir, Bella Alvarez, Jean A. Niles, Lissenya B. Argueta, Kathryn A. Shelton, Sarah Kezar, Pramod N. Nehete, Dora M. Berman, Melissa A. Willman, Xian C. Li, Camillo Ricordi, Joan E. Nichols, A. Osama Gaber, Norma S. Kenyon and Alessandro Grattoni ()
Additional contact information
Jesus Paez-Mayorga: Houston Methodist Research Institute
Jocelyn Nikita Campa-Carranza: Houston Methodist Research Institute
Simone Capuani: Houston Methodist Research Institute
Nathanael Hernandez: Houston Methodist Research Institute
Hsuan-Chen Liu: Houston Methodist Research Institute
Corrine Ying Xuan Chua: Houston Methodist Research Institute
Fernanda Paola Pons-Faudoa: Houston Methodist Research Institute
Gulsah Malgir: Houston Methodist Research Institute
Bella Alvarez: Houston Methodist Research Institute
Jean A. Niles: Houston Methodist Research Institute
Lissenya B. Argueta: Houston Methodist Research Institute
Kathryn A. Shelton: MD Anderson Cancer Center
Sarah Kezar: MD Anderson Cancer Center
Pramod N. Nehete: MD Anderson Cancer Center
Dora M. Berman: University of Miami
Melissa A. Willman: University of Miami
Xian C. Li: Houston Methodist Hospital
Camillo Ricordi: University of Miami
Joan E. Nichols: Houston Methodist Research Institute
A. Osama Gaber: Houston Methodist Hospital
Norma S. Kenyon: University of Miami
Alessandro Grattoni: Houston Methodist Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35629-z

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