High Mobility Group Proteins in Tissue Regeneration

Abstract

Cartilage damage and treatment thereof are major issues for patients of all ages as well as companion animals such as the dog. The tissue engineering based autologous chondrocyte transplantation (ACT) employs in vitro amplification of explanted chondrocytes for subsequent transplantation into the damaged area to grow new cartilage. Enhancements include factors improving cell growth as well as scaffolds providing the cells with growth conditions mimicking their natural localisation in the extracellular cartilage matrix. This thesis focuses on chondrocyte proliferation induced by the embryonic high mobility group AT-hook (HMGA) proteins and derivatives thereof. Further work aims at evaluating beta-tricalcium phosphate (B-TCP) scaffolds for the prospective use in canine cartilage repair, as well as at comparative genetics of selected canine high mobility group (HMG) genes. The results have shown significantly increased chondrocyte proliferation by application of recombinant HMGA proteins or a synthetically produced fragment of HMGA2, respectively. Furthermore, B-TCP scaffolds have been proven biocompatible for seeding with highly vital isolated canine chondrocytes that interact with and integrate well into the macro- and microstructure of the constructs. Finally, analyses of canine HMG genes have revealed high similarity to their human orthologues. Concluding, the results of this thesis open up new possibilities of HMGA-assisted cartilage regeneration in tissue engineering, including chondrocyte-seeded scaffolds. The high similarity of human and canine HMG genes facilitates knowledge transfer of HMGA-based tissue engineering approaches between both species.