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Treatment of diabetes by islet cell transplantation

Objective

The long-term goal of this programme is to cure diabetic patients by implantation of insulin-producing islet cells.
The long term goal of this programme is to prevent the development of chronic complications in diabetic patients by implantation of an insulin producing beat graft cell.
Our working hypothesis is that successful transplantation of beta cell grafts with selected size, composition and function. The biologic properties of beta cell grafts should be characterised and adjusted to the metabolic and immunologic status of the recipient. This type of graft should increase the efficacy of accompanying measures aiming at graft survival and/or metabolic correction.
Since the supply of human beat cels is insufficient for experimental or therapeutic trnasplantation programmes in diabetes, we propose additional core activities for the production of beta graft cells from two alternate sources. The first approach aims at the generation of human beta cells from stem cells which are to be purified frompancreatic duct cells that will be isolatedfrom young donors. The secon approach involves mass isolation of islet or beta cells from foetal porcine pancreata and their encapsulation in bioartificial devices which protect the xenogeneic donor tissue agianst host attack.
The project is based on the observation that purified endocrine islet cell grafts correct the diabetic state in rodents and remain functional across a major histocompatibility barrier without continuous pharmacologic immunosuppression. Implantation of unpurified pancreatic tissue or organs is, on the contrary, markedly less successful in the treatment of diabetes, even under immunosuppressive drug administration. Islet cell preparations also allow quantitative and qualitative assessment of the biologic properties of donor material. This is considered important for constructing metabolically and immunologically adequate grafts. Therefore, purified insulin-producing cell grafts will be prepared from human pancreatic organs and maintained in an islet cell bank. Isolated insulin-producing B cells will be made available to participating research laboratories for studies focusing on the cellular, metabolic and immunologic questions of this programme. After satisfactory quality control, the grafts will be implanted in selected insulin-dependent diabetic patients.

This multinational initiative involves collection of human donor pancreata by participating centres, their shipment to the central facility in Brussels for the standardized production and banking of grafts, and the distribution of quality-tested material to participating hospitals for clinical trial. All stages in the project require interactions between research and clinical departments. Parallel collaborations in research and development focus on medical and technological issues of this programme.

Coordinator

The Vrije Universiteit
Address
Laarbeeklaan 103
1090 Brussels
Belgium