Biology of the islet graft transplanted into the submucosal space of the hamster
[Thesis]
N. Tchervenivanov
L. Rosenberg
McGill University (Canada)
1995
155
M.Sc.
McGill University (Canada)
1995
The purpose of this study was to determine if islets of Langerhans transplanted into the submucosal compartment of the duodenum survive after implantation, and to establish their replication rate. Our goal was also to evaluate both the number of islets needed to achieve normoglycemia in diabetes and the potential of the implant to maintain glucose homeostasis. Experiments were performed using Syrian hamsters. Islets of Langerhans were obtained by collagenase digestion of pancreata and purified on a BSA gradient. Following transplantation, islet morphology and insulin synthesis were maintained. Normoglycemia was not achieved in hyperglycemic animals transplanted with <800 islets, but was achieved in 8/11 diabetic animals transplanted with usd\geusd800 islets. Reversal of hyperglycemia occurred over 2-5 weeks. The usd\betausd-cells remained well-granulated in recipients of usd\geusd800 islets and euglycemia was maintained until sacrifice up to 20 weeks post-transplantation. Glucose utilization was similar in normoglycemic controls and in recipients of usd\geusd800 islets, but was significantly impaired in all diabetic animals. In conclusion, (1) the submucosal space supports islet graft viability at least up to 20 weeks post-implantation, (2) the grafts function to reverse the diabetic state, but (3) a critical islet cell mass is necessary to reverse hyperglycemia and maintain normal glucose homeostasis. The submucosal space of the duodenum appears to be an effective site for islet implantation, but additional studies are required to further evaluate the benefits.