Superoxide dismutase and catalase significantly improve the osteogenic differentiation potential of osteogenetically compromised human adipose tissue-derived stromal cells in vitro

Abstract

Mesenchymal stromal cells (MSCs) play a pivotal role in modern therapeutic approaches of bone defect regeneration. A complication that is steadily increasing due to demographic population developments is an age-related disorder of the osteogenic differentiation potential (ODP) of MSCs. In the present in vitro study we have evaluated the impact of reactive oxygen species (ROS) and antioxidants on ODP of “normal healthy” as well as osteogenetically compromised human adipose tissue-derived stromal cells (ASC). We show that although ASC exhibit a marked ODP, a significant number of ASC cultures showed a retarded osteogenesis. These so-called “non-responder”-ASC cultures (NR-ASC) expressed an antigenic phenotype identical to that of the well osteogenically differentiating “responder”-ASCs (R-ASC), but NR-ASC significantly correlated with the older age of their donors as well as with a significantly higher intracellular generation of ROS. Furthermore, we found that treatment of the cell cultures with low concentration of H2O2 seemed to promote osteogenic differentiation but higher H2O2 concentration strongly reduced osteogenesis in all ASC cultures. Additionally, we found that exogenously applied superoxide dismutase (SOD) or catalase completely restored the impaired ODP of NR-ASC, whereas ascorbate, glutathione, N-acetylcysteine or a water soluble vitamin E derivate did not show any relevant effects. Our results suggest that aging-related increases in oxidative stress, especially due to H2O2, can severely impair the ODP of ASC whereas SOD or catalase almost completely corrected this disorder. Our findings point to novel osteo-therapeutic aspects of catalase and SOD and open up new approaches to ASC-based regeneration of bone defects.