title: Impact of an autologous oxygenating matrix culture system on rat islet transplantation outcome.
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 (Integrinβ1, p-FAK/FAK, p-Akt/Akt), survival (caspase 3, TUNEL, FDA/PI), function, and HIF-1α translocation were assessed. Afterwards, P-matrices were dissolved and the islets were intraportally transplanted. 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-1α 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.
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France.
authors.forename: A
authors.initials: A
authors.lastname: Schaschkow
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Mura
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France.
authors.forename: W
authors.initials: W
authors.lastname: Bietiger
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Peronet
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France.
authors.forename: A
authors.initials: A
authors.lastname: Langlois
authors.affiliation: Service de chirurgie Plastique et maxillo faciale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Bodin
authors.affiliation: Service de chirurgie Plastique et maxillo faciale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Dissaux
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France; Service de chirurgie Plastique et maxillo faciale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Bruant-Rodier
authors.affiliation: Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: M
authors.initials: M
authors.lastname: Pinget
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France; Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: N
authors.initials: N
authors.lastname: Jeandidier
authors.affiliation: Department of Vascular Surgery, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: M T
authors.initials: MT
authors.lastname: Juszczak
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Sigrist
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France. Electronic address: e.pedracini@ceed-diabete.org.
authors.forename: E
authors.initials: E
authors.lastname: Maillard
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D005466:Fluorocarbons / Q000378:metabolism; D006085:Graft Survival; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar
chemical_list: D005466:Fluorocarbons; C008805:perfluorodecalin; D010100:Oxygen
keywords: IBMIR; Intraportal transplantation; Perfluorodecalin; Plasma matrix; Type 1 diabetes