Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 12 2022
26 12 2022
Historique:
received:
22
01
2022
accepted:
14
12
2022
entrez:
26
12
2022
pubmed:
27
12
2022
medline:
29
12
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36572684
doi: 10.1038/s41467-022-35629-z
pii: 10.1038/s41467-022-35629-z
pmc: PMC9792517
doi:
Substances chimiques
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7951Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK132104
Pays : United States
Informations de copyright
© 2022. The Author(s).
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