Development of an ectopic site for islet transplantation, using biodegradable scaffolds.
Clinical islet transplantation in liver has achieved normoglycemia. However, this site may not be ideal for islet survival. To create a more optimal site for islet transplantation, we have developed a construct with biodegradable scaffolds. Islets were seeded in scaffolds and transplanted into the epididymal fat pad of diabetic BALB/c mice. Controls included islets transplanted underneath the kidney capsule or into the fat pad without scaffolds. All animals with islets in scaffolds or the kidney became normoglycemic and maintained this metabolic state. When islets were transplanted without scaffolds the time to achieve normoglycemia was significantly increased and less than 45% of mice survived. An oral glucose tolerance test was performed on the scaffold and kidney groups with similar blood glucose levels and area under the curve values between the groups. Grafts were removed at more than 100 days posttransplantation and all animals became hyperglycemic. There was no significant difference in insulin content between the grafts and all grafts were well vascularized with insulin-positive beta cells. Therefore, islets in scaffolds function and restore diabetic animals to normoglycemic levels, similar to islets transplanted underneath the kidney capsule, suggesting scaffolds can be used to create a site for islet transplantation.
Dufour
Jannette M
JM
Surgical-Medical Research Institute, University of Alberta, Edmonton, AB, Canada.
Rajotte
Ray V
RV
Zimmerman
Mark
M
Rezania
Alireza
A
Kin
Tatsuya
T
Dixon
Doreen E
DE
Korbutt
Gregory S
GS
D000818:Animals; D019540:Area Under Curve; D001672:Biocompatible Materials / Q000378:metabolism; D001673:Biodegradation, Environmental; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000601:surgery*; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D005215:Fasting; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D005951:Glucose Tolerance Test; D006085:Graft Survival; D006943:Hyperglycemia / Q000503:physiopathology; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000601:surgery; D007797:Laminin / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011098:Polyglactin 910 / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011509:Proteoglycans / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D016042:Transplantation, Heterotopic / Q000379:methods* / Q000502:physiology*; D014184:Transplantation, Homologous
D001672:Biocompatible Materials; D001786:Blood Glucose; D004338:Drug Combinations; D007328:Insulin; D007797:Laminin; D011108:Polymers; D011509:Proteoglycans; C059485:matrigel; D011098:Polyglactin 910; D003094:Collagen; D005934:Glucagon; D005947:Glucose