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 GaberNorma S. Kenyon, Alessandro Grattoni

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number7951
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

Fingerprint

Dive into the research topics of 'Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats'. Together they form a unique fingerprint.

Cite this