title: Dual factor delivery of CXCL12 and Exendin-4 for improved survival and function of encapsulated beta cells under hypoxic conditions.
abstract: A bioartifical pancreas (BAP) remains a promising approach for treating insulin-dependent diabetes. Several obstacles to the clinical implementation of a BAP remain, including hypoxia following implantation. Within native pancreatic islets, CXCL12 and glucagon-like peptide-1 (GLP-1) act in a paracrine fashion to promote the survival, function, and proliferation of β-cells. This work sought to investigate if the presentation of CXCL12 and delivery of a GLP-1 receptor analog, Exendin-4 (Ex-4), alone and in combination, conferred pro-survival and insulinotropic effects on an encapsulated β-cell line, βTC-tet, cultured under hypoxic conditions of 7.6 mmHg O2 . Our findings indicate that presentation of CXCL12 in the encapsulation matrix completely abrogated apoptosis under hypoxic conditions. Delivery of Ex-4 increased insulin secretion rate under both normoxic and hypoxic conditions, and additionally reduced apoptosis under hypoxic conditions. Furthermore, presentation of CXCL12 combined with Ex-4 delivery significantly increased insulin secretion rate under hypoxic conditions compared to delivery of Ex-4 alone. These findings demonstrate that the presentation of CXCL12 combined with the delivery of Ex-4 may constitute a promising strategy for supporting β-cell function and survival following transplantation.
authors: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, Georgia, USA.
authors: Stephanie
authors: S
authors: Duncanson
authors: Athanassios
authors: A
authors: Sambanis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018914:Cells, Immobilized; D054377:Chemokine CXCL12 / Q000378:metabolism*; D000077270:Exenatide; D000860:Hypoxia; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D051379:Mice; D019397:Pancreas, Artificial; D010455:Peptides / Q000378:metabolism*; D014688:Venoms / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide