Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 14, Issue 7, Pages 1523-1532Publisher
WILEY
DOI: 10.1111/ajt.12742
Keywords
Bioengineering; islet xenotransplantation; regenerative medicine; type 1 diabetes mellitus
Categories
Funding
- MRSEC program at the Materials Research Center of the National Science Foundation [NSF DMR-1121262]
- Nanoscale Science and Engineering Center of the National Science Foundation [EEC-0118025/003]
- State of Illinois
- Northwestern University
- US Army Research Office
- US Army Medical Research and Materiel Command
- National Institutes of Health (NIH) through the National Institutes of Biomedical Imaging and Bioengineering (NIBIB) [R01EB009910]
- National Institutes of General Medical Sciences (NIGMS) [T32 GM008449]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [F30 DK084649]
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Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designed to enhance islet engraftment and function. We investigated localized trophic factor delivery in a xenogeneic human islet to mouse model of islet transplantation. Double emulsion microspheres containing exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a layered scaffold design consisting of porous outer layers for islet transplantation and a center layer for sustained factor release. Protein encapsulation and release were dependent on both the polymer concentration and the identity of the protein. Proteins retained bioactivity upon release from scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing scaffolds demonstrated significant improvement and prolongation of graft function relative to blank scaffolds carrying no protein, and the release profile significantly impacted the duration over which the graft functioned. Ex4-releasing scaffolds enabled better glycemic control in animals subjected to an intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4-delivering scaffolds provide an extrahepatic transplantation site for modulating the islet microenvironment to enhance islet function posttransplant.
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