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A subcutaneous pancreatic islet transplantation platform using a clinically applicable, biodegradable Vicryl mesh scaffold - an experimental study

Komatsu, Hirotake and Gonzalez, Nelson and Salgado, Mayra and Cook, Colin A. and Liu, Junfeng and Rawson, Jeffrey and Omori, Keiko and Tai, Yu-Chong and Kandeel, Fouad and Mullen, Yoko (2020) A subcutaneous pancreatic islet transplantation platform using a clinically applicable, biodegradable Vicryl mesh scaffold - an experimental study. Transplant International, 33 (7). pp. 806-818. ISSN 0934-0874. https://resolver.caltech.edu/CaltechAUTHORS:20200331-101551849

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Abstract

Pancreatic islet transplantation into the liver is an effective treatment for type 1 diabetes but has some critical limitations. The subcutaneous site is a potential alternative transplant site, requiring minimally invasive procedures and allowing frequent graft monitoring; however, hypoxia is a major drawback. Our previous study without scaffolding demonstrated post‐transplant graft aggregation in the subcutaneous site, which theoretically exacerbates lethal intra‐graft hypoxia. In this study, we introduce a clinically applicable subcutaneous islet transplantation platform using a biodegradable Vicryl mesh scaffold to prevent aggregation in a diabetic rat model. Islets were sandwiched between layers of clinically proven Vicryl mesh within thrombin‐fibrin gel. In vitro, the mesh prevented islet aggregation and intra‐islet hypoxia, which significantly improved islet viability. In vivo rat syngeneic islet transplantations into a prevascularized subcutaneous pocket demonstrated that the mesh significantly enhanced engraftment, as measured by assays for graft survival and function. Histological examination at six weeks showed well‐vascularized grafts sandwiched in a flat shape between the mesh layers. The biodegradable mesh was fully absorbed by three months, which alleviated chronic foreign body reaction and fibrosis, and supported long‐term graft maintenance. This simple graft shape modification approach is an effective and clinically applicable strategy for improved subcutaneous islet transplantation.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1111/tri.13607DOIArticle
ORCID:
AuthorORCID
Komatsu, Hirotake0000-0003-0876-4809
Cook, Colin A.0000-0002-6283-5105
Tai, Yu-Chong0000-0001-8529-106X
Additional Information:© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd. Issue Online: 27 June 2020; Version of Record online: 14 April 2020; Accepted manuscript online: 21 March 2020; Manuscript accepted: 17 March 2020; Manuscript revised: 27 December 2019; Manuscript received: 07 December 2019. Funding Information: Nora Eccles Treadwell Foundation.
Funders:
Funding AgencyGrant Number
Nora Eccles Treadwell FoundationUNSPECIFIED
Subject Keywords:biodegradable mesh scaffold; hypoxia; oxygenation; pancreatic islet; subcutaneous cell transplantation; Vicryl mesh
Issue or Number:7
Record Number:CaltechAUTHORS:20200331-101551849
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200331-101551849
Official Citation:Komatsu, H., Gonzalez, N., Salgado, M., Cook, C.A., Li, J., Rawson, J., Omori, K., Tai, Y.‐C., Kandeel, F. and Mullen, Y. (2020), A subcutaneous pancreatic islet transplantation platform using a clinically applicable, biodegradable Vicryl mesh scaffold ‐ an experimental study. Transpl Int, 33: 806-818. doi:10.1111/tri.13607
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102195
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:31 Mar 2020 17:36
Last Modified:02 Jul 2020 15:57

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