Journal
TRANSPLANTATION
Volume 85, Issue 10, Pages 1456-1464Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e31816fc0ea
Keywords
islet transplantation; biomaterial; diabetes; PLG; scaffold; microenvironment
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Funding
- NIBIB NIH HHS [F31 EB 007118, R01 EB003806-04, R01 EB003806, F31 EB007118-02, R01 EB 003806, F31 EB007118] Funding Source: Medline
- NIDDK NIH HHS [R01 DK 52919, R21 DK 067833, R21 DK063439, R21 DK067833, R01 DK 062641, R01 DK 063439, R21 DK062641] Funding Source: Medline
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Background. The survival and function of transplanted pancreatic islets is limited, owing in part to disruption of islet-matrix attachments during the isolation procedure. Using polymer scaffolds as a platform for islet transplantation, we investigated the hypothesis that replacement of key extracellular matrix components known to surround islets in vivo would improve graft function at an extrahepatic implantation site. Methods. Microporous polymer scaffolds fabricated from copolymers of lactide and glycolide were adsorbed with collagen IV, fibronectin, laminin-332 or serum proteins before seeding with 125 mouse islets. Islet-seeded scaffolds were then implanted onto the epididymal fat pad of syngeneic mice with streptozotocin-induced diabetes. Nonfasting glucose levels, weight gain, response to glucose challenges, and histology were used to assess graft function for 10 months after transplantation. Results. Mice transplanted with islets seeded onto scaffolds adsorbed with collagen IV achieved euglycemia fastest and their response to glucose challenge was similar to normal mice. Fibronectin and laminin similarly promoted euglycemia, yet required more time than collagen IV and less time than serum. Histopathological assessment of retrieved grafts demonstrated that coating scaffolds with specific extracellular matrix proteins increased total islet area in the sections and vessel density within the transplanted islets, relative to controls. Conclusions. Extracellular matrix proteins adsorbed to microporous scaffolds can enhance the function of transplanted islets, with collagen IV maximizing graft function relative to the other proteins tested. These scaffolds enable the creation of well-defined microenvironments that promote graft efficacy at extrahepatic sites.
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