title: Co-encapsulation of bioengineered IGF-II-producing cells and pancreatic islets: effect on beta-cell survival.
abstract: Insulin-like growth factor-II (IGF-II) has been shown to promote pancreatic β-cell survival. We evaluated the effect of co-encapsulating islets and bioengineered IGF-II-producing cells on islet cell survival. IGF-II or green fast protein (GFP) genes were transferred into TM4 cells, and purified using a neomycin resistance gene, leading to pure cell cultures (TM4-IGF-II or TM4-GFP) with a stable overexpression of the transferred gene. Islets were co-encapsulated with TM4-IGF-II or TM4-GFP, or encapsulated alone in alginate microcapsules. Rat and mouse islet cell survival was studied in vitro and in vivo, respectively. After 12 days in culture, islet viability (dual staining, acridine orange/propidium iodide) was 83% with TM4-IGF-II, compared with 51% (P<0.05) and 41% (P<0.001) with TM4-GFP and islets alone, respectively. The study of islet necrotic centers and the evaluation of islet function, using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay, yielded similar results. From 125 days after transplantation, more diabetic mice maintained normoglycemia when they were transplanted with islets co-encapsulated with TM4-IGF-II (4/7). A significant difference for the maintenance of normoglycemia was observed between recipients of islets co-encapsulated with TM4-IGF-II versus islets alone (P=0.023), or with TM4-GFP (P=0.048). In conclusion, the co-encapsulation of islets with bioengineered IGF-II-producing cells promotes islet cell survival.
authors.affiliation: Research Laboratory on Bioartificial Therapies, Maisonneuve-Rosemont Hospital Research Centre, Université de Montréal, Montréal, Québec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Jourdan
authors.forename: J
authors.initials: J
authors.lastname: Dusseault
authors.forename: P Y
authors.initials: PY
authors.lastname: Benhamou
authors.forename: L
authors.initials: L
authors.lastname: Rosenberg
authors.forename: J P
authors.initials: JP
authors.lastname: Hallé
mesh_terms: D000818:Animals; D002214:Capsules; D002460:Cell Line; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D049452:Green Fluorescent Proteins / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D050417:Insulin-Secreting Cells; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D051381:Rats
chemical_list: D002214:Capsules; D049452:Green Fluorescent Proteins; D007335:Insulin-Like Growth Factor II