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

Author

Listed:
  • Jesus Paez-Mayorga

    (Houston Methodist Research Institute
    Tecnologico de Monterrey)

  • Jocelyn Nikita Campa-Carranza

    (Houston Methodist Research Institute
    Tecnologico de Monterrey)

  • Simone Capuani

    (Houston Methodist Research Institute
    University of the Chinese Academy of Sciences (UCAS), Shijingshan)

  • 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
    Tecnologico de Monterrey)

  • 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
    The University of Texas Graduate School of Biomedical Sciences at Houston)

  • Dora M. Berman

    (University of Miami
    University of Miami)

  • Melissa A. Willman

    (University of Miami)

  • Xian C. Li

    (Houston Methodist Hospital
    Houston Methodist Hospital)

  • Camillo Ricordi

    (University of Miami)

  • Joan E. Nichols

    (Houston Methodist Research Institute
    Houston Methodist Hospital)

  • A. Osama Gaber

    (Houston Methodist Hospital)

  • Norma S. Kenyon

    (University of Miami
    University of Miami
    University of Miami
    University of Miami)

  • Alessandro Grattoni

    (Houston Methodist Research Institute
    Houston Methodist Hospital
    University of Miami
    Houston Methodist Hospital)

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.

Suggested Citation

  • 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 , 2022. "Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35629-z
    DOI: 10.1038/s41467-022-35629-z
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    References listed on IDEAS

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    1. Giacomo Bruno & Nicola Di Trani & R. Lyle Hood & Erika Zabre & Carly Sue Filgueira & Giancarlo Canavese & Priya Jain & Zachary Smith & Danilo Demarchi & Sharath Hosali & Alberto Pimpinelli & Mauro Fer, 2018. "Unexpected behaviors in molecular transport through size-controlled nanochannels down to the ultra-nanoscale," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Long-Hai Wang & Alexander Ulrich Ernst & Duo An & Ashim Kumar Datta & Boris Epel & Mrignayani Kotecha & Minglin Ma, 2021. "A bioinspired scaffold for rapid oxygenation of cell encapsulation systems," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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