Extracellular matrix protein-coated scaffolds promote the reversal of diabetes after extrahepatic islet transplantation.
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.
Salvay
David M
DM
Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208-3120, USA.
Rives
Christopher B
CB
Zhang
Xiaomin
X
Chen
Fei
F
Kaufman
Dixon B
DB
Lowe
William L
WL
Shea
Lonnie D
LD
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006085:Graft Survival; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011184:Postoperative Period; D054457:Tissue Scaffolds
D001786:Blood Glucose; D016326:Extracellular Matrix Proteins