Glutathione-Allylsulfur Conjugates as Mesenchymal Stem Cells Stimulating Agents for Potential Applications in Tissue Repair.

The endogenous gasotransmitter H ₂ S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H ₂ S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H ₂ S-releasing agents on the growth of stem cells have not been fully investigated. H ₂ S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H ₂ S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H ₂ S agents on the cell growth and differentiation of cardiac Lin ^- Sca1 ⁺ human mesenchymal stem cells (cMSC) and on normal human dermal fibroblasts (NHDF). In particular, we investigated the effects of water-soluble GSH-garlic conjugates (GSGa) on cMSC compared to other H ₂ S-releasing agents, such as Na ₂ S and GYY4137. GSGa treatment of cMSC and NHDF increased their cell proliferation and migration in a concentration dependent manner with respect to the control. GSGa treatment promoted an upregulation of the expression of proteins involved in oxidative stress protection, cell-cell adhesion and commitment to differentiation. These results highlight the effects of H ₂ S-natural donors as biochemical factors that promote MSC homing, increasing their safety profile and efficacy after transplantation, and the value of these donors in developing functional 3D-stem cell delivery systems for cardiac muscle tissue repair and regeneration.