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When a cell or an organ is transplanted, the immune system will attack the transplanted graft and try to get rid of it. By using an alginate capsule as an immunoisolating barrier, we believe that it is possible to transplant cells without the use of immunosuppressives that increase the risk of infection and cancer. Many diseases are caused by the body's inability to produce the necessary amount of a needed molecule, such as a hormone, receptor or enzyme. Cell therapy thus offers enormous potential for the treatment of numerous diseases including diabetes, cancer, Parkinson's disease and hypocalcaemia.

Alginate is a group of extremely long polysaccharides found in seaweed and in some bacteria. In seaweed its function is to provide both stability and strength to the plant. Alginate consists of 50 to 200 000 units of the two sugar molecules mannuronic acid (M) and guluronic acid (G). Alginate forms gels with ions such as Ca²⁺ and Ba²⁺ under physiological conditions. Blocks of repeating G units (G-blocks) form cavities that bind the cations which cross-link G-blocks of other alginate chains. Hence, G-block sequences are required for the alginate to form a gel with divalent ions. The composition of M and G and the length of the alginate chain determine the properties of the alginate. By revealing the link between composition and function, it is therefore possible to control the properties of the alginate gel. In addition to alginate production in seaweed, alginate is produced extracellularly by Azotobacter vinelandii and some Pseudomonas species. The final step in alginate biosynthesis is the formation of G-residues in the mannuronan polymer chain. This conversion, or epimerisation, of M to G is catalyzed by enzymes known as mannuronan C-5 epimerases. Seven mannuronan C-5 epimerases from A. vinelandii have been cloned, sequenced and expressed in Escherichia coli by the Molecular Genetics group here at NTNU. The epimerases have different product specificity as some make short G-blocks, some make long G-blocks, some make MG-blocks and some make mixtures of G-blocks and MG-blocks. Hence, novel alginates with desired structures can be made. This makes it possible to enzymatically tailor alginate for different uses. In microcapsule formation, G-blocks are important to form cross-links with the divalent ions. However, we have seen that the enzymatic conversion of M-blocks to MG-blocks may be favorable. Introduction of these flexible segments results in reduced size, better stability and reduced permeability of the microcapsules.

Insulin dependent diabetes mellitus (IDDM, also called type I diabetes) is regarded as an autoimmune disease which results in destruction of the insulin producing ß-cells of the pancreas. Despite insulin therapy, many IDDM patients may develop complications such as unawareness of hypoglycaemia, nephropathy, neuropathy and retinopathy. One alternative treatment of IDDM is to provide the patient with insulin producing tissue by transplantation. Whole pancreas or islet transplantation is the only treatment to achieve and maintain long-term normoglycaemia, without the need for exogenous insulin treatment. However, the transplanted tissue will be susceptible to immune-mediated destruction if the recipient is not given immunosuppressants. Whole pancreas transplantation alone is a complicated surgical procedure and is only given to a limited numbers of IDDM patients. Transplantation of only the pancreatic islets seems to be an attractive approach since it does not require major surgery. The success rate of islet transplantation in man was low until the change of procedure by the Edmonton protocol in 2000 which lifted the success rate of islet transplantation from about 10% to 100% one year after transplantation for the first 7 patients. Over time, however, the number of insulin independent patients is reduced, partly due to toxicity of the immunosuppressive drugs. The use of alginate microcapsules may eliminate the need for immunosuppressants and hence reduce the risk of infections.
Another obstacle is the currently limited supply of human pancreas, and the fact that two or three pancreas are necessary to obtain enough islets for one transplantation. One way to solve this problem is to utilize islet from porcine, which in principle represents a large source of cells. However, the use of xenotransplantation may require a stronger immune barrier surrounding the transplant. In addition, the possibility of virus transmission from donor to the recipient must be evaluated.

In Norway there are around 300-400 new cases of primary brain tumors (gliomas) each year. These gliomas constitute around 50% of the total number of intracranial tumors where the malignant forms have a very bad prognosis with a mean survival of around 1 year. Despite intensive research the treatment of patients with gliomas has not improved during the last 40 years and the survival rate after treatment has not increased. Thus, there is a demanding need for new therapy for this disease. During the last 10 years recombinant gene technology has made it possible to transfect cells with genes encoding proteins, which may suppress the growth and development of the gliomas. The use of these cells for transplantation purposes has been hampered by immune-mediated destruction of the cells. Encapsulating these production cells in alginate can solve this. The aim is to develop a biological therapy system, which consists of different types of producer cells encapsulated in alginate. Our group has established collaboration with Professor Rolf Bjerkvig at the University of Bergen, who has been working with experimental animal models for gliomas for several years.

The results from these projects should give important information on how to construct and produce biocompatible alginate capsules which can be used for allo- and xeno transplantation. This technology may provide new treatments for insulin dependent diabetes mellitus as well as for malignant gliomas.