Impact of an autologous oxygenating matrix culture system on rat islet transplantation outcome A. Schaschkow a , C. Mura a , W. Bietiger a , C. Peronet a , A. Langlois a , F. Bodin d , C. Dissaux d , C. Bruant-Rodier a, d , M. Pinget b , N. Jeandidier a, b , M.T. Juszczak c , S. Sigrist a , E. Maillard a, * a UMR DIATHEC, EA 7294, Centre Europ een d’Etude du Diab ete, Universit e de Strasbourg, F ed eration de M edecine Translationnelle de Strasbourg, Bld Ren e Leriche, Strasbourg, France b Structure d’Endocrinologie, Diab ete-Nutrition et Addictologie, P^ ole NUDE, H^ opitaux Universitaires de Strasbourg, Strasbourg, France c Department of Vascular Surgery, John Radcliffe Hospital, Oxford, United Kingdom d Service de chirurgie Plastique et maxillo faciale, H^ opitaux Universitaires de Strasbourg, Strasbourg, France article info Article history: Received 15 October 2014 Accepted 1 February 2015 Available online Keywords: Type 1 diabetes Plasma matrix Perfluorodecalin IBMIR Intraportal transplantation abstract Disruption of the pancreatic islet environment combined with the decrease in oxygen supply that occurs during isolation leads to poor islet survival. The aim of this study was to validate the benefit of using a plasma-based scaffold supplemented with perfluorodecalin to improve islet transplantation outcome. Rat islets were cultured in three conditions: i) control group, ii) plasma based-matrix (P-matrix), and iii) P-matrix supplemented with emulsified perfluorodecalin. After 24 h culture, matrix/cell contacts (Integrinb1, p-FAK/FAK, p-Akt/Akt), survival (caspase 3, TUNEL, FDA/PI), function, and HIF-1a trans- location were assessed. Afterwards, P-matrices were dissolved and the islets were intraportally trans- planted. Graft function was monitored for 31 days with glycaemia and C-peptide follow up. Inflammation was assessed by histology (macrophage and granulocyte staining) and thrombin/anti-thrombin complex measurement. Islet survival correlated with an increase in integrin, FAK, and Akt activation in P-matrices and function was maintained. Perfluorodecalin supplementation decreased translocation of HIF-1a in the nucleus and post-transplantation islet structure was better preserved in P-matrices, but a quicker activation of IBMIR resulted in early loss of graft function. “Oxygenating” P-matrices provided a real benefit to islet survival and resistance in vivo. However, intraportal transplantation is not suitable for this kind of culture due to IBMIR; thus, alternative sites must be explored. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Pancreatic islet transplantation has proven to be a successful cell therapy for reversing life-threatening hypoglycaemic unawareness for type 1 diabetic patients [1,2]. However, several pancreases are required to obtain sufficient engrafted islet mass to reach insulin- independence in a single patient. Indeed, the number of isolated islets falls dramatically during the process of isolation and trans- plantation because they are weakened by hypoxia, anoïkis, and the inflammatory coupled with thrombotic reaction (IBMIR) [3e6]. Pancreatic islets represent only 2% of the whole pancreas. They are complex structures composed of different cell types with spe- cific function in glycaemia regulation and are often compared to mini organs scattered in the pancreatic tissue. To ensure glycaemic control, islets are vascularized by a rich network [7] of vessels providing nutrient supply, hormone transport, and a high oxygen partial pressure (~40 mm Hg) [8]. To preserve islet structure, con- tacts with the surrounding tissue are maintained by integrin re- ceptors such as the b1 integrin subunit. The structural role of b1 Abbreviations: ECM, extra-cellular matrix; ePFD, Emulsified perfluorodecalin; FAK, Focal Adhesion Kinase; FDA, Fluorescein Diacetate; HIF-1a, Hypoxia-inducible factor 1a; IBMIR, Instant Blood Mediated Inflammatory Reaction; PI, Propidium iodide; PI3K/Akt, Phosphatidylinositol-3 0 -kinase/Protein kinase B; PV, Portal vein; STZ, Streptozotocin; TAT, ThrombineAntithrombin complex; TUNEL, Terminal deoxynucleotidyl transferaseemediated dUTP nick-end labelling. * Corresponding author. E-mail address: e.pedracini@ceed-diabete.org (E. Maillard). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials http://dx.doi.org/10.1016/j.biomaterials.2015.02.031 0142-9612/© 2015 Elsevier Ltd. All rights reserved. Biomaterials 52 (2015) 180e188