Islet transplantation
Principal Investigator
Olle Korsgren, Uppsala University
Olle.Korsgren@klinimm.uu.se
Research area description
A significant progress in the field of ß cell replacement therapy can only be made based on an increased understanding of the processes governing post-transplantation islet survival and engraftment. Two main routes are perused to fill this gap in knowledge:
- Experimental studies in relevant animal models.
- Establishment of new techniques to allow detailed characterization of the processes regulating islet survival and engraftment in humans.
In both experimental and clinical studies different sites of implantation will be evaluated, "pros and cons" of the intraportal route of islet administration will be carefully scrutinized and compared head-to-head with alternative sites of implantation.
An efficient step-wise screening program for the identification of approaches and drugs suitable to promote islet survival and engraftment has been established. Via a series of in vitro models, in small animals and pre-clinical large animals, we have already identified several substances, with a marked capacity to control innate immunity (IBMIR). We have in academic regimes successfully developed these substances into novel drugs at present evaluated in clinical trials or awaiting final regulatory approval.
Similarly, using the same step-wise screening program we have established powerful quantitative and qualitative diagnostic tools, the FDG PET-CT scans and the high resolution MR technique, for evaluation of islet survival and distribution after clinical intraportal and intramuscular islet transplantation. Hence, we feel confident that the established step-wise screening program constitute an indispensable tool for promoting development in clinical islet transplantation.
The driving force in the development of "a new endocrine organ" at an extrahepatic site is the creation of composite Endothelial Cell-Mesenchymal Stem Cell -islet grafts combined with different biodegradable scaffolds decorated with growth factors, drugs and oxygen carriers.
The large size of the Nordic Network for Clinical Islet transplantation (annually about 40 batches of islets are released for transplantation) is a prerequisite for conducting randomized clinical trials to evaluate any novel approach in clinical islet transplantation.
The successful completion of the proposed studies would establish ß cell replacement therapy for patients with type I diabetes. Procedures and drugs developed to optimize islet survival as well as diagnostic tools defined and validated will be of immense importance not only for clinical islet transplantation but also for future stem cell therapy.