American Diabetes Association
Browse
1/1
3 files

Intracutaneous Transplantation of Islets within a Biodegradable Temporizing Matrix (BTM) as an Alternative Site for Islet Transplantation

figure
posted on 2023-03-22, 13:29 authored by Darling Rojas-Canales, Stacey N. Walters, Daniella Penko, Daniele Cultrone, Jacqueline Bailey, Tatyana Chtanova, Jodie Nitschke, Julie Johnston, Svjetlana Kireta, Thomas Loudovaris, Thomas W Kay, Tim R. Kuchel, Wayne Hawthorne, Philip J. O’Connell, Greg Korbutt, John E. Greenwood, Shane T. Grey, Chris J. Drogemuller, P.Toby Coates

  

Intra-hepatic islet transplantation for type-1 diabetes is limited by the need for multiple infusions and poor islet viability post-transplantation. The development of alternative transplantation sites is necessary to improve islet survival, and facilitate monitoring and retrieval. We tested a clinically proven Biodegradable Temporizing Matrix (BTM), a polyurethane-based scaffold, to generate a well vascularized intracutaneous ‘neo-dermis’ within the skin for islet transplantation.  In murine models, BTM did not impair syngeneic islet renal-subcapsular transplant viability or function, and facilitated diabetes cure for over 150 days. Further, BTM supported functional neonatal porcine islet transplants into RAG-1-/- mice for 400 days. Hence, BTM is non-toxic for islets. two-photon intravital imaging used to map vessel growth through time identified dense vascular networks, with significant collagen deposition and increases in vessel mass up to 30 days post-BTM implantation. In a pre-clinical porcine skin model, BTM implants created a highly-vascularized intracutaneous site by day 7 post-implantation. When syngeneic neonatal porcine islets were transplanted intracutaneously the islets remained differentiated as insulin producing cells, maintained normal islet architecture, secreted c-peptide, and survived for over 100 days. Here we show that BTM facilitates formation of an islet-supportive intracutaneous ‘neo-dermis’ in a porcine pre-clinical model, as an alternative islet transplant site.

Funding

This work was supported by JDRF International SRA-2016-257-S-B and the Hospital Research Foundation, South Australia. It was presented at the International Pancreas and Islet Transplantation Association meeting in Lyon, France in July 2019.

History

Usage metrics

    Diabetes

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC