Abstract
Articular cartilage has a limited ability to heal. Mesenchymal stem cells (MSCs) derived from the bone marrow have shown promise as a cell type for cartilage regeneration strategies. In this study, sodium tungstate (Na(2)WO(4)), which is an insulin mimetic, was evaluated for the first time as an inductive factor to enhance human MSC chondrogenesis. MSCs were seeded onto three-dimensional electrospun scaffolds in growth medium (GM), complete chondrogenic induction medium (CCM) containing insulin, and CCM without insulin. Na(2)WO(4) was added to the media leading to final concentrations of 0, 0.01, 0.1, and 1 mM. Chondrogenic differentiation was assessed by biochemical analyses, immunostaining, and gene expression. Cytotoxicity using human peripheral blood mononuclear cells (PBMCS) was also investigated. The chondrogenic differentiation of MSCs was enhanced in the presence of low concentrations of Na(2)WO(4) compared to control, without Na(2)WO(4). In the induction medium containing insulin, cells in 0.01 mM Na(2)WO(4) produced significantly higher sulfated glycosaminoglycans, collagen type II, and chondrogenic gene expression than all other groups at day 28. Cells in 0.1 mM Na(2)WO(4) had significantly higher collagen II production and significantly higher sox-9 and aggrecan gene expression compared to control at day 28. Cells in GM and induction medium without insulin containing low concentrations of Na(2)WO(4) also expressed chondrogenic markers. Na(2)WO(4) did not stimulate PBMC proliferation or apoptosis. The results demonstrate that Na(2)WO(4) enhances chondrogenic differentiation of MSCs, does not have a toxic effect, and may be useful for MSC-based approaches for cartilage repair.