Microencapsulation – the Trondheim work

The Trondheim work is based on more than fifty years of alginate research. Gudmund Skjåk-Bræk and Terje Espevik from NTNU were part of the first clinical trials with encapsulated islets for the treatment of Type 1 diabetes in 1994. Based on experience with fibrosis on alginate-polylysine capsules and knowledge on alginate structure-function relationships, Berit L. Strand suggested an alginate bead based on a high-G alginate gelled in a mix of calcium and barium and without polycation to be used in the CDP. Alginate beads had been shown previously to be protecting islets against rejection both in allo- and xenotransplantation in rodents and within the CDP we showed that the alginate beads could protect human islets in mice. However, the success was very limited in monkeys, due to fibrotic overgrowth of the capsules that reduce the function and viability of the encapsulated cells. We have, since the first monkey studies in 2006 and together within the CDP tried to find the cause of the fibrosis on alginate beads, and while many questions are solved on the way, this still remains unsolved. In addition to the studies in the whole blood model by Dr. Anne Mari Rokstad, we have lately performed proteomics studies of proteins adsorbed to the capsule surface and also worked on chemical modification of alginates as a tool to make new capsule materials. Chemical modification and enzymatic modification are powerful toolboxes for tailoring the alginate to new functionalities. From the proteomics studies, we see that different capsule types have different protein adsorption profiles and we do see a match with the absorbed proteins to what we have experienced by antibody staining of specific proteins. The proteins may give us new hints of the molecular mechanisms causing the fibrosis on the alginate beads. Indeed, we do experience that our toolbox of chemical modification of the alginate results in specific patterns of protein adsorption as well as capsules without cells attached in the C57Bl/6 mice model.