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Transpl Int. 2020 Mar 21. doi: 10.1111/tri.13607. [Epub ahead of print]

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

Author information

1
Department of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.
2
Department of Electrical Engineering, California Institute of Technology, 1200 E. California Blvd., MC 136-93, Pasadena, CA, 91125, USA.

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.

KEYWORDS:

Subcutaneous cell transplantation; Vicryl mesh; biodegradable mesh scaffold; hypoxia; oxygenation; pancreatic islet

PMID:
32198960
DOI:
10.1111/tri.13607

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