Pancreas and islet cell transplantation

Currently, for the patient with type 1 diabetes, a definitive treatment without resorting to the use of exogenous insulin can be achieved only with pancreas or islet cell transplantation. These means of restoring β-cell mass can completely maintain essentially normal long-term glucose homeostasis, although the need for powerful immunosuppressive regimens limits their application to only a subgroup of adult patients. Apart from the shortage of donors that has limited all kinds of transplantation, however, the widespread use of β-cell replacement has been precluded until recently by the drawbacks associated with both organ and islet cell transplantation. Although the study of recurrence of diabetes has generated attention, the fundamental obstacle to pancreas and islet transplantation has been, and remains, the alloimmune response. With a better elucidation of the mechanisms of alloengraftment achieved during the last 3 years, the stage has been set for further advances

Comparison of Four Pancreatic Islet Implantation Sites

Although the liver is the most common site for pancreatic islet transplantation, it is not optimal. We compared kidney, liver, muscle, and omentum as transplantation sites with regard to operative feasibility, and the efficiency of implantation and glycemic control. Islets from C57BL/6 mice were transplanted into diabetic syngeneic recipients. The mean operative time and mortality were measured to assess feasibility. To assess implantation efficiency, the marginal mass required to cure diabetes and the mean time taken to achieve normoglycemia were measured. A glucose tolerance test was performed to assess glycemic control efficiency. The data are listed in the order of the kidney, liver, muscle, and omentum, respectively. The mean mortality rate was 6.7, 20.0, 7.1, and 12.5%; the mean operative time was 10.2, 27.4, 11.2, and 19.8 min; the marginal islet mass was 100, 600, 600, and 200 islet equivalence units and the mean time to reach euglycemia was 3.0, 15.1, 26.6, and 13.9 days. The glucose kinetics of omental pouch islets was the most similar to controls. Thus, a strategic approach is required for deciding on the best transplantation recipient sites after considering donor sources and islet volume. Alternatives can be chosen based on safety or efficacy

Biology of the islet graft transplanted into the submucosal space of the hamster

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 $ge$800 islets. Reversal of hyperglycemia occurred over 2-5 weeks. The $beta$-cells remained well-granulated in recipients of $ge$800 islets and euglycemia was maintained until sacrifice up to 20 weeks post-transplantation. Glucose utilization was similar in normoglycemic controls and in recipients of $ge$800 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