Islet Transplantation

Experimental islet transplantation started more than 3 decades ago with the discovery that islets of Langerhans could be separated from the pancreatic tissue with collagenase. Islet allotransplantation could potentially replace pancreas transplantation for the treatment of Type 1 diabetics. Islet autotransplantation can be used to prevent diabetes mellitus following a major pancreatectomy. As of today 400-500 islet allotransplantations and 200-300 autotransplantations have been performed worldwide.

The success of islet transplantation in humans is limited, with no more than 20% of patients achieving complete normalization of glucose metabolism. The long-term function of transplanted islets has been poor with most grafts showing deterioration in function within 5 years. 

The main obstacles to successful islet transplantation are: a) relatively small beta cell mass available after islet purification, b) autoimmune and alloimmune islet cell destruction, c) current use of diabetogenic immunosuppressants.

The main mode of islet transplantation consists of intraportal embolization. Other potential sites for transplantation include the spleen and the kidney capsule.

The morphological aspects of allo- and autoimmune islet graft destruction are well known through experimental studies. These consist of lymphocytic isletitis and eventual disappearance of the hormone producing cells. In clinical practice tissue evaluation is not used for the diagnosis of islet rejection. In experimental studies sophisticated methods for the detection of islet rejection have included the demonstration in serum of elevated levels of endogenous islet proteins and daily sequential intravenous glucose tolerance tests.

In addition to islet transplantation, other strategies for treatment of type I diabetes are being investigated. These include fetal pancreas transplants, genetically engineered beta-cell lines and gene therapy, implanted insulin pumps and artificial pancreas units. Xenotransplantation (i.e. porcine islets) or in vitro expansion of cultured beta-cells could in theory represent the solution for the problem of limited pool of islet tissue for transplantation.

 

References

1. Federlin KF, Jahr H, Bretzel RG: Islet transplantation as treatment of type 1 diabetes: from experimental beginnings to clinical application. Exp Clin Endocrinol Diabetes 2001;109Suppl2:S373-83
2. Gray DW: Islet transplantation and glucose regulation. World J Surg 2001;25:497-502.
3. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000;343:289-90.
4. Ryan EA, Lakey JR, Rajotte RV, Korbutt GS, Kin T, Imes S et al.: Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes 2001;50:710-9.
5. Cretin N, Caulfield A, Fournier B, Buhler L, Becker C, Philippe J, Morel P: Insulin independence and normalization of oral glucose tolerance test after islet cell allotransplantation. Transpl Int 2001;14:343-5.
6. Stegall MD, Lafferty KJ, Kam I, Gill RG: Evidence of recurrent autoimmunity in human allogeneic islet transplantation. Transplantation 1996;61:1272-4.
7. Oberholzer J, Triponez F, Lou J, Morel P: Clinical islet transplantation: A review. Ann N Y Acad Sci 1999;875:189-99.
8. Inoue K, Miyamoto M: Islet transplantation. J Hepatobiliary Pancreat Surg 2000;7:163-7.
9. Sutherland DE: Pancreas and islet transplantation: now and then. Transplant Proc 1996;28:2131-3.
10. Menger MD, Yamauchi J, Vollmar B: Revascularization and microcirculation of freely grafted islets of Langerhans. Worl J Surg 2001;25:509-15.
11. Shapiro AM, Hao EG, Lakey JR, Yakimets WJ, Churchill TA, Mitlianga, PG, et al.: Novel approach toward early diagnosis of islet allograft rejection. Transplantation 2001;71:1709-18.