title: Impact of Pancreatic Rat Islet Density on Cell Survival during Hypoxia.
abstract: In bioartificial pancreases (BP), the number of islets needed to restore normoglycaemia in the diabetic patient is critical. However, the confinement of a high quantity of islets in a limited space may impact islet survival, particularly in regard to the low oxygen partial pressure (PO2) in such environments. The aim of the present study was to evaluate the impact of islet number in a confined space under hypoxia on cell survival. Rat islets were seeded at three different concentrations (150, 300, and 600 Islet Equivalents (IEQ)/cm(2)) and cultured in normal atmospheric pressure (160 mmHg) as well as hypoxic conditions (15 mmHg) for 24 hours. Cell viability, function, hypoxia-induced changes in gene expression, and cytokine secretion were then assessed. Notably, hypoxia appeared to induce a decrease in viability and increasing islet density exacerbated the observed increase in cellular apoptosis as well as the loss of function. These changes were also associated with an increase in inflammatory gene transcription. Taken together, these data indicate that when a high number of islets are confined to a small space under hypoxia, cell viability and function are significantly impacted. Thus, in order to improve islet survival in this environment during transplantation, oxygenation is of critical importance.
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez-Brotons
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 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, 67200 Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Peronet
authors.affiliation: Defymed, avenue Dante, 67200 Strasbourg, France.
authors.forename: J
authors.initials: J
authors.lastname: Magisson
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Sookhareea
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: A
authors.initials: A
authors.lastname: Langlois
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 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, 67200 Strasbourg, France; Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg (HUS), 67000 Strasbourg, France.
authors.forename: N
authors.initials: N
authors.lastname: Jeandidier
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France; Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg (HUS), 67000 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, 67200 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, 67200 Strasbourg, France.
authors.forename: E
authors.initials: E
authors.lastname: Maillard
mesh_terms: D000818:Animals; D017209:Apoptosis; D001274:Atmospheric Pressure; D015687:Cell Hypoxia; D002470:Cell Survival; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D017208:Rats, Wistar; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D016207:Cytokines; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D010100:Oxygen
references.citation: Transplantation. 2003 Jul 27;76(2):290-6
references.pmid: 12883181
references.citation: Anesthesiology. 2003 Feb;98(2):387-95
references.pmid: 12552198
references.citation: J Biol Chem. 1987 Aug 5;262(22):10712-7
references.pmid: 2440873
references.citation: Diabetes. 1993 Jan;42(1):12-21
references.pmid: 8420809
references.citation: Transplantation. 1994 Apr 15;57(7):1017-20
references.pmid: 8165697
references.citation: Diabetes. 1998 Jul;47(7):1027-32
references.pmid: 9648824
references.citation: J Mol Med (Berl). 1999 Jan;77(1):93-5
references.pmid: 9930937
references.citation: Transplantation. 1999 Mar 15;67(5):665-71
references.pmid: 10096520
references.citation: Cell Transplant. 2005;14(7):441-8
references.pmid: 16285252
references.citation: J Biomech Eng. 2005 Dec;127(7):1054-61
references.pmid: 16502647
references.citation: Theor Biol Med Model. 2009;6:5
references.pmid: 19371422
references.citation: Curr Opin Organ Transplant. 2009 Dec;14(6):688-93
references.pmid: 19745734
references.citation: Diabetes Obes Metab. 2010 Oct;12 Suppl 2:159-67
references.pmid: 21029313
references.citation: Biomaterials. 2011 Sep;32(26):5945-56
references.pmid: 21676459
references.citation: Theor Biol Med Model. 2011;8:20
references.pmid: 21693022
references.citation: Cell Transplant. 2011;20(9):1333-42
references.pmid: 21294962
references.citation: Cell Death Dis. 2012;3:e322
references.pmid: 22695615
references.citation: Diabetes Care. 2012 Jul;35(7):1436-45
references.pmid: 22723582
references.citation: World J Gastroenterol. 2012 Dec 21;18(47):6885-93
references.pmid: 23322985
references.citation: Cell Transplant. 2012;21(4):657-69
references.pmid: 21944582
references.citation: Ann N Y Acad Sci. 2013 Apr;1281:16-35
references.pmid: 23323860
references.citation: Pathobiology. 2013;80(4):194-202
references.pmid: 23652283
references.citation: Cell Transplant. 2013;22(7):1137-46
references.pmid: 23043940
references.citation: Cell Transplant. 2013;22(8):1463-76
references.pmid: 23043896
references.citation: Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):19054-8
references.pmid: 24167261
references.citation: Diabetes. 2014 May;63(5):1433-44
references.pmid: 24757193
references.citation: J Diabetes Res. 2014;2014:405362
references.pmid: 24963494
references.citation: Diabetes. 2014 Oct;63(10):3221-9
references.pmid: 24947356
references.citation: Curr Pharm Biotechnol. 2014;15(7):590-608
references.pmid: 25219869
references.citation: PLoS One. 2014;9(10):e107656
references.pmid: 25343247
references.citation: Cell Transplant. 2015;24(12):2505-12
references.pmid: 25375416
references.citation: Am J Transplant. 2006 Nov;6(11):2791-5
references.pmid: 16939517
references.citation: Cell Transplant. 2006;15(8-9):745-58
references.pmid: 17269445
references.citation: Biotechnol Bioeng. 2007 Apr 1;96(5):990-8
references.pmid: 16897784
references.citation: J Biol Chem. 2004 Jan 2;279(1):765-71
references.pmid: 14576162