The authors have no conflict of interest to declare.
Dual factor delivery of CXCL12 and Exendin-4 for improved survival and function of encapsulated beta cells under hypoxic conditions†
Article first published online: 26 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 110, Issue 8, pages 2292–2300, August 2013
How to Cite
Duncanson, S. and Sambanis, A. (2013), Dual factor delivery of CXCL12 and Exendin-4 for improved survival and function of encapsulated beta cells under hypoxic conditions. Biotechnol. Bioeng., 110: 2292–2300. doi: 10.1002/bit.24872
- Issue published online: 25 JUN 2013
- Article first published online: 26 MAR 2013
- Accepted manuscript online: 21 FEB 2013 08:11AM EST
- Manuscript Accepted: 8 FEB 2013
- Manuscript Revised: 6 FEB 2013
- Manuscript Received: 6 DEC 2012
- NIH. Grant Numbers: R01 DK076801, T32 GM008433
- βTC-tet cells;
- bioartificial pancreas
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. Biotechnol. Bioeng. 2013; 110: 2292–2300. © 2013 Wiley Periodicals, Inc.