Title:
Therapy of IDDM with microencapsulated porcine islets of Langerhans - Improvement of the xenograft and its long-term function
Project management at the University of Würzburg:
Participating scientists:
Abstract:
Our long-term goal is to provide a functional, healthful islet graft from the pig for the therapy of patients who suffer from insulin-dependent diabetes mellitus ("Xenogeneic Islet Transplantation"). To avoid the life-long immunosuppression of young diabetics, immunoisolation of isolated porcine islets of Langerhans using biocompatible alginates will be pursued and evaluated. In this funding period, we aim for the reliable, long-term reversion of a chemically-induced (Streptozotozin) diabetes in rats using barium-alginate-microen-capsulated islets of Langerhans from the pig: we will try to achieve long-term islet graft function for more than 365 days in over 70% of the animal recipients, without immunosuppression. At present, only 33% of the microencapsulated islet xenografts survive and function for 150 - 500 days. The remaining xenografts are either not accepted at all (27%) or suffer from acute rejection (40%). In the process of optimizing the graft function, we plan to improve the isolation process, the microencapsulation (material and technology), the in vitro culture and function of porcine islets of Langerhans, as well as the analysis of the specific and unspecific immune reactions of the recipient to the graft. We are confident to reach this goal due to our promising results obtained during the previous funding periods. This project should lay the groundwork for future preclinical trials in non-human primates.
Key words:
diabetes mellitus
encapsulation
alginate
xenotransplantation
islets of Langerhans
Projekt period: from 05.1999 to 04.2004
Funding institution:
Landeshaushalt Wissenschaftsministerium
Bund
Publications:
Links:
Experimental Transplantation Immunology (ETI)
D3 on the surgery web site