title: Comparison of Perfluorodecalin and HEMOXCell as Oxygen Carriers for Islet Oxygenation in an In Vitro Model of Encapsulation.
abstract: Transplantation of encapsulated islets in a bioartificial pancreas is a promising alternative to free islet cell therapy to avoid immunosuppressive regimens. However, hypoxia, which can induce a rapid loss of islets, is a major limiting factor. The efficiency of oxygen delivery in an in vitro model of bioartificial pancreas involving hypoxia and confined conditions has never been investigated. Oxygen carriers such as perfluorocarbons and hemoglobin might improve oxygenation. To verify this hypothesis, this study aimed to identify the best candidate of perfluorodecalin (PFD) or HEMOXCell®to reduce cellular hypoxia in a bioartificial pancreas in an in vitro model of encapsulation ex vivo. The survival, hypoxia, and inflammation markers and function of rat islets seeded at 600 islet equivalents (IEQ)/cm2and under 2% pO2were assessed in the presence of 50 μg/mL of HEMOXCell or 10% PFD with or without adenosine. Both PFD and HEMOXCell increased the cell viability and decreased markers of hypoxia (hypoxia-inducible factor mRNA and protein). In these culture conditions, adenosine had deleterious effects, including an increase in cyclooxygenase-2 and interleukin-6, in correlation with unregulated proinsulin release. Despite the effectiveness of PFD in decreasing hypoxia, no restoration of function was observed and only HEMOXCell had the capacity to restore insulin secretion to a normal level. Thus, it appeared that the decrease in cell hypoxia as well as the intrinsic superoxide dismutase activity of HEMOXCell were both mandatory to maintain islet function under hypoxia and confinement. In the context of islet encapsulation in a bioartificial pancreas, HEMOXCell is the candidate of choice for application in vivo.
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .
authors: Aida
authors: A
authors: Rodriguez-Brotons
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .
authors: William
authors: W
authors: Bietiger
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .
authors: Claude
authors: C
authors: Peronet
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .
authors: Allan
authors: A
authors: Langlois
authors: 3 Defymed , Strasbourg, France .
authors: Jordan
authors: J
authors: Magisson
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .
authors: Carole
authors: C
authors: Mura
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .
authors: Cynthia
authors: C
authors: Sookhareea
authors: 4 HEMARINA Aéropôle Centre , Biotechnopôle, Morlaix, France .
authors: Valerie
authors: V
authors: Polard
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .|2 Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg (HUS) , Strasbourg, France .
authors: Nathalie
authors: N
authors: Jeandidier
authors: 4 HEMARINA Aéropôle Centre , Biotechnopôle, Morlaix, France .
authors: Franck
authors: F
authors: Zal
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .|2 Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg (HUS) , Strasbourg, France .
authors: Michel
authors: M
authors: Pinget
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .
authors: Séverine
authors: S
authors: Sigrist
authors: 1 Université de Strasbourg, Centre Européen d'Etude du Diabète, Strasbourg, France .
authors: Elisa
authors: E
authors: Maillard
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000493:pharmacokinetics / Q000494:pharmacology; D005466:Fluorocarbons / Q000493:pharmacokinetics / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000493:pharmacokinetics / Q000494:pharmacology; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001802:Blood Substitutes; D005466:Fluorocarbons; C008805:perfluorodecalin; D010100:Oxygen
keywords: bioartificial pancreas; hypoxia; insulin; islet; oxygen carriers