Islet transplantation: present and future perspectives

Abstract

Islet cell transplantation can potentially normalize blood glucose levels and stop the progression of clinical complications, and if the transplant is done early in the course of the disease complications may be prevented. Remarkable progress has been made in recent years and islet cell transplantation has resulted in normalization of metabolic control in several patients with Type 1 diabetes in the absence of hypoglycemia. Only a few patients, however, have achieved insulin independence. Issues relating to islet cell engraftment within the liver, prevention of rejection and recurrent autoimmunity, and identification of alternative immunosuppressive drugs that do not adversely affect islet cell function remain to be solved. Thus far, the need for chronic, generalized immunosuppression to prevent rejection of the islets has limited the indication to those patients who have already received another transplant or to those who simultaneously receive islets and another organ (generally a kidney). Identification of immunointervention protocols that allow for engraftment in the absence of deleterious effects on the islets and prevent rejection and recurrent autoimmunity would make this procedure suitable for all patients, including children who have not yet developed long-term complications of the disease.

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“…Islets were isolated using the method described by Ricordi 10 (Figures 1 and 2). A central incision into the pancreas was performed, and 2 cannulae were inserted into the main pancreatic ducts.…”

“…After centrifugation, the interface containing the islets was removed and prepared for yield and purity. [10][11][12][13] Viability was measured by combined fluorescent dye staining with propidium iodide and fluorescein diacetate. Then, the islets cultured in CMRL media and maintained in a humidified incubator at 30°C with 5% CO 2 .…”

Adenovirus-Mediated CTLA4Ig or CD40Ig Gene Transfer Delays Pancreatic Islet Rejection in a Rat-to-Mouse Xenotransplantation Model after Systemic but Not Local Expression

“…Costimulatory blockade has resulted in long-term survival or tolerance in several but not enoviruses by PCR amplification of the E1 adenoviral region. all cases of islet allotransplantation (18,27,36) and xenotransplantation (10,26,35). The association of CTLA4Ig…”

“…level required to inhibit a mixed lymphocyte reaction (37), and this did not result in a longer graft survival DISCUSSION compared with the other animals from this group. Analysis of production in tissues after transplantation of Costimulatory blockade is able to inhibit rejection of both allogeneic (18,27,30,36) and xenogeneic islets (10, AdCTLA4Ig-transduced islets in animals also receiving IM AdCD40Ig, using the 4F10 anti-CTLA4 antibody, 26,35) and combinations of CD28 and CD40 blockade can induce donor-specific tolerance in some but not all confirmed the local production of CTLA4Ig (data not shown). In the association of AdCTLA4Ig-transduced conditions (6,24,38).…”

Hepatic Insulin Gene Therapy in Insulin-Dependent Diabetes Mellitus

“…Pancreas or islet transplantation are effective functional therapies that can reverse metabolic abnormalities and prevent or minimize many of the secondary complications of IDDM, but their clinical applicability are limited by the scarce supply of available organs. Furthermore, to overcome the rapid and aggressive reoccurrence of autoimmunity against b-cells, life-long immunosuppression is required (7,8).…”