Objectives: $LThe main objectives for this project are: Bioengineering of pancreatic beta cell surrogate cells on the basis of insulinoma cells; bioengineering of surrogate cells on the basis of somatic cells (i.e. fibroblasts); bioengineering of insulin producing cells with other favourable properties, such as cells that are protected against autoimmune mediated destruction during development of diabetes and analysis of the feasibility of the bioengineered cells for insulin replacement and reversal of diabetic state.
Diabetes mellitus is a metabolic disorder with a crippling socio-economic impact. It affects about 5 % of the population in European countries. The disease is becoming increasingly prevalent amongst the aged and it is associated with severe late complications causing serious morbidity and premature mortality.
Molecular biology is a potent new tool which now permits the generation of novel insulin-producing tissue culture cell lines, in which the structures essential for stimulus-secretion coupling can be modified in a well-defined manner. Suitably engineered insulin-secreting cells can be implanted into diabetic animals thus providing a physiological form of insulin replacement therapy. In a second step, somatic cells (e.g. fibroblasts) can be taken also from the patient, bioengineered to generate insulin-secreting cells, and returned to the patient. This approach overcomes many of the problems associated with tissue availability and immune üülrejection encountered with conventional therapy. In addition, it will be possible with these new methods of genetic engineering to modify also other properties of insulin-creating cells such as an improved glucose recognition and signaling pathway and an increased resistance towards destruction which make them more feasible as surrogates.
In this "Concerted Action", the cumulative expertise of the leading European islet diabetes researchers is gathered to provide all cellular and molecular biology methods required to generate a successful gene therapy approach to insulin delivery. The long-term perspective is a novel approach for the treatment and cure of diabetes. Such an achievement in diabetes therapy would have a substantial impact upon general health in Europe.
Diabetes mellitus, IDDM, gene therapy, bioengineered cells, insulin delivery, pancreatic beta cells, insulin biosynthesis, insulin secretion