Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation.
BACKGROUND
Problems associated with the hepatic transplantation of islets may preclude the broad application of islet transplantation. Thus, we sought to develop an approach to the extrahepatic transplantation of islets using a synthetic biodegradable polymer scaffold.


METHODS
Microporous polymer scaffolds that allow vascular ingrowth and nutrient diffusion from host tissues were fabricated from copolymers of lactide and glycolide. Murine islets were transplanted without or with a scaffold onto intraperitoneal fat of syngeneic diabetic recipients. Bioluminescence imaging using a cooled charge-coupled device camera, immunohistochemistry, and glycemia were used to assess islet engraftment and function posttransplant.


RESULTS
By bioluminescence imaging, islets transplanted on a polymer scaffold remain localized to the transplant site and survive for an extended period of time. Islets transplanted on scaffolds retained the architecture of native islets and developed a functional islet vasculature. Transplantation of marginal masses of islets on the polymer scaffold demonstrated improved islet function compared to transplantation without a scaffold as assessed by the effectiveness of diabetes reversal, including mean time required to achieve euglycemia, weight gain, and glucose levels during an intraperitoneal glucose tolerance test.


CONCLUSIONS
These findings indicate that a synthetic polymer scaffold can serve as a platform for islet transplantation and improves the function of extrahepatically transplanted islets compared to islets transplanted without a scaffold. The scaffold may also be useful to deliver bioactive molecules to modify the microenvironment surrounding the transplanted islets and, thus, enhance islet survival and function.
Blomeier
Herman
H
Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Zhang
Xiaomin
X
Rives
Christopher
C
Brissova
Marcela
M
Hughes
Elizabeth
E
Baker
Marshall
M
Powers
Alvin C
AC
Kaufman
Dixon B
DB
Shea
Lonnie D
LD
Lowe
William L
WL
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D005951:Glucose Tolerance Test; D006085:Graft Survival; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000098:blood supply; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers; D013311:Streptozocin
D011108:Polymers; D013311:Streptozocin