Figure 2.

Recipient T-lymphocytes govern Mesenchymal stem cell (MSC)-based bone regeneration via IFN-γ and TNF-α. Recipient T-cells secrete IFN-γ to inhibit osteogenic differentiation of implanted MSCs by inducing Smad6/Runx2 signaling and TNF-α to trigger apoptotic pathway via activation of caspase 8 and caspase 3. However, a combination of IFN-γ and TNF-α treatment initiates FAS internalization and accelerates caspase 8/3 apoptotic process. As a novel strategy to improve MSC-mediated bone regeneration, local administration of aspirin or systemic infusion of Tregs can reduce the levels of IFN-γ and TNF-α, thereby protecting implanted MSCs from recipient T-cell attack.