Enhancing inflammatory and chemotactic signals to regulate bone regeneration.

Stem cells have become the fundamental element in regenerative medicine due to their inherent potential to differentiate into various cell types, and the ability to produce various bioactive molecules, including growth factors, cytokines and extracellular matrix molecules. In vivo, the secretion of tropic factors is modulated by chemotactic and inflammatory factors. In this study, we analysed the influence of a 2 h stimulation of mesenchymal stem cells (MSCs) with interleukin-1β (IL1β), granulocyte-colony stimulating factor (GCSF), stromal cell-derived factor 1 (SDF1) and stem cell factor (SCF). Our results demonstrated that this short stimulation exerts pronounced effects on the expression of multiple cytokine genes and proteins in MSC cells 48 and 72 h later. IL1β strongly promoted the secretion of a wide range of proteins with chemotactic, proinflammatory and angiogenic properties, whereas SCF regulated the expression of proteins involved in proliferation, chondrogenesis and ECM regulation. This demonstrates that the changes in secretome can be directed towards a desired final functional outcome by selection of the most appropriate cytokine. Moreover, the expression pattern of Wnt signalling pathway components suggested the differential regulation of this pathway by IL1β and SCF. Altogether, the robust paracrine action of MSCs can be achieved within a just 2 h treatment, which would be feasible within the operating theatre during a single surgical procedure. These results suggest that integrating inflammatory modulation in bone tissue engineering, by modifying the MSC secretome by way of a short stimulus, would provide a more targeted approach than administering unmodified MSCs alone.