Antioxidative defense, differentiation and regeneration potential of tissue specific mesenchymal stem cells during ageing

Adult mesenchymal stem cells (MSCs) exhibit ex vivo high proliferation and multilineage differentiation potential and are considered important for cell therapy either in autologous or allogeneic transplantation setting. The goal of our project is to determine influence of ageing and putative impairment of antioxidative defense to differentiation and regeneration potential of human, dog and experimental animals tissue specific MSCs. MSCs will be harvested from dental pulp and tissues connected with a development of tooth, synovial fluid, bone marrow and subcutaneous adipose tissue from young and elderly donors. Immunophenotype, antioxidative defense, cellular stress response, proliferation and chondrogenic, osteogenic and neurogenic differentiation potential during in vitro cultivation will be compared between different age groups. Effects of IL-6, antioxidants or low oxygen concentration on MSCs will be evaluated both, in adherent and suspension cultures. Regeneration potential of MSCs will be evaluated on arteficial cartilage, bone and neural tissue defects on laboratory animals. MSCs based osteoarthritis therapy in dogs will be evaluated on clinical cases. We expect to demonstrate that differences in tissue specific MSCs characteristics during ageing are related to impairement of antioxidative defense system and that allotransplantation of MSCs from young donors could improve therapy of cartilage, cranial and axial bones and neural tissue defects.