Influence of microenvironment on engraftment of transplanted β-cells

Pancreatic islet transplantation into the liver provides a possibility to treat selected patients with brittle type 1 diabetes mellitus. However, massive early β-cell death increases the number of islets needed to restore glucose homeostasis. Moreover, late dysfunction and death contribute to the poor long-term results of islet transplantation on insulin independence. Studies in recent years have identified early and late challenges for transplanted pancreatic islets, including an instant blood-mediated inflammatory reaction when exposing human islets to the blood microenvironment in the portal vein and the low oxygenated milieu of islets transplanted into the liver. Poor revascularization of remaining intact islets combined with severe changes in the gene expression of islets transplanted into the liver contributes to late dysfunction. Strategies to overcome these hurdles have been developed, and some of these interventions are now even tested in clinical trials providing a hope to improve results in clinical islet transplantation. In parallel, experimental and clinical studies have, based on the identified problems with the liver site, evaluated the possibility of change of implantation organ in order to improve the results. Site-specific differences clearly exist in the engraftment of transplanted islets, and a more thorough characterization of alternative locations is needed. New strategies with modifications of islet microenvironment with cells and growth factors adhered to the islet surface or in a surrounding matrix could be designed to intervene with site-specific hurdles and provide possibilities to improve future results of islet transplantation

Islet transplantation in type I diabetes mellitus

Hintergrund Die Inseltransplantation entwickelte sich in den letzten 15 Jahren für eine Auswahl von Patienten mit Diabetes mellitus Typ 1 zu einer etablierten Therapieoption. Fragestellung Indikationsstellung, mögliche Varianten sowie Langzeitresultate der Inseltransplantation sollten aufgezeigt werden. Material und Methoden Die zur Verfügung stehenden Arbeiten zum kurz- und langfristigen Verlauf nach Inseltransplantation wurden zusammengestellt und bewertet. Ergebnisse Mit der Inseltransplantation werden hinsichtlich Glukosekontrolle [HbA1c (Hämoglobin Typ A1c)], Reduktion von Hypoglykämien und Erhaltung der Funktion der transplantierten Niere mit der Pankreastransplantation vergleichbare Resultate erzielt. Während eine langfristige Insulinunabhängigkeit trotz multipler konsekutiver Transplantationen nur selten erreicht wird, ist das Auftreten von transplantationsassoziierten Komplikationen deutlich geringer als bei der Pankreastransplantation. Diskussion Für Patienten mit schlechter Glukosekontrolle und rezidivierenden schweren Hypoglykämien sowie für Patienten mit geplanter Nierentransplantation sollte eine Insel- oder Pankreastransplantation erwogen werden, bei Patienten mit hohem perioperativem Risiko ist Erstere die Therapie der Wahl gegenüber der Pankreastransplantation. = Background Islet transplantation has become an established treatment option for a selected, small number of patients with type 1 diabetes mellitus. Objectives Indication, options, and long-term results of islet transplantation are presented. Materials and methods A compilation of original work on short- and long-term results after islet transplantation is reviewed. Results With islet transplantation, results regarding glucose control (HbA1c), reduction of hypoglycemia, and preservation of function of the transplanted kidney are comparable to pancreas transplantation. While long-term insulin independence is not achieved in most cases despite multiple transplantations, the occurrence of transplantation-associated complications is much lower compared to pancreas transplantation. Conclusions For patients with poor glycemic control and recurrent severe hypoglycemia, and for patients with a planned kidney transplantation, islet or pancreas transplantation should be evaluated. The former is the preferred option for patients with a high perioperative risk

Challenges in pancreas transplantation

Whole-organ pancreas transplantation, either alone or combined with a kidney transplant, is the only definitive treatment for many patients with type 1 diabetes that restores normal glucose homoeostasis and insulin independence. Pancreas transplantation delays, or potentially prevents, secondary diabetes complications and is associated with improvement in patient survival when compared with either patients remaining on the waiting list or those receiving kidney transplant alone. Pancreas transplantation is safe and effective, with 1-year patient survival >97 % and graft survival rates of 85 % at 1 year and 76 % at 5 years in recent UK data. This review focuses on some current areas of interest in pancreas transplantation