title: Extracellular matrix components supporting human islet function in alginate-based immunoprotective microcapsules for treatment of diabetes.
abstract: In the pancreas, extracellular matrix (ECM) components play an import role in providing mechanical and physiological support, and also contribute to the function of islets. These ECM-connections are damaged during islet-isolation from the pancreas and are not fully recovered after encapsulation and transplantation. To promote the functional survival of human pancreatic islets, we tested different ECMs molecules in alginate-encapsulated human islets. These were laminin derived recognition sequences, IKVAV, RGD, LRE, PDSGR, collagen I sequence DGEA (0.01 - 1.0 mM), and collagen IV (50 - 200 µg/mL). Interaction with RGD and PDSGR promoted islet viability and glucose induced insulin secretion (GIIS) when it was applied at concentrations ranging from 0.01 - 1.0 mM (p < 0.05). Also the laminin sequence LRE contributed to enhanced GIIS but only at higher concentrations of 1 mM (p < 0.05). Collagen IV also had beneficial effects but only at 50 µg/ml and no further improvement was observed at higher concentrations. IKVAV and DGEA had no effects on human islets. Synergistic effects were observed by adding Collagen(IV)-RGD, Collagen(IV)-LRE, and Collagen(IV)-PDSGR to encapsulated human islets. Our results demonstrate the potential of specific ECM components in support of functional survival of human encapsulated and free islet grafts. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1788-1796, 2016.
authors.affiliation: Department of Pathology and Medical Biology, Immunoendocrinology, University of Groningen, Hanzeplein 1, Groningen, RB, 9700, The Netherlands.
authors.forename: Alberto
authors.initials: A
authors.lastname: Llacua
authors.affiliation: Department of Pathology and Medical Biology, Immunoendocrinology, University of Groningen, Hanzeplein 1, Groningen, RB, 9700, The Netherlands.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: de Haan
authors.affiliation: Department of Pathology and Medical Biology, Immunoendocrinology, University of Groningen, Hanzeplein 1, Groningen, RB, 9700, The Netherlands.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Smink
authors.affiliation: Department of Pathology and Medical Biology, Immunoendocrinology, University of Groningen, Hanzeplein 1, Groningen, RB, 9700, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002214:Capsules; D002470:Cell Survival / Q000187:drug effects; D024141:Collagen Type IV / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000628:therapy*; D005109:Extracellular Matrix / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology
chemical_list: D000464:Alginates; D002214:Capsules; D024141:Collagen Type IV; D006603:Hexuronic Acids; D007328:Insulin; D007797:Laminin; D010455:Peptides; D020723:Glucuronic Acid; D005947:Glucose
keywords: encapsulation; extracellular matrix; glucose-induced insulin secretion; laminin; pancreatic islets