Abstract
The endogenous gasotransmitter H2S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H2S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H2S-releasing agents on the growth of stem cells have not been fully investigated. H2S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H2S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H2S 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 H2S-releasing agents, such as Na2S 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 H2S-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.
Highlights
The gasotransmitter H2S is a physiological signalling molecule in mammalian cells that stimulates important molecular pathways [1,2,3]
We investigated the antioxidant properties of GSH–garlic conjugates (GSGa), demonstrating its ability to inhibit cell death induced by ROS damage or CoCl2 in cardiac Lin− Sca1+ human mesenchymal stem cells (cMSC) and normal human dermal fibroblasts (NHDF)
The protective effect of H2S by the oxidative stress was well investigated in the human cells using NaHS as H2S donor [1,41], the effects of potential nutraceutical bio-products, such as GSGa, on MSC has not yet been assessed
Summary
The gasotransmitter H2S is a physiological signalling molecule in mammalian cells that stimulates important molecular pathways [1,2,3]. The allylsulfides DADS and DATS, which are the major components of oil-soluble garlic extract, are H2S slow-releasing donors. Their intracellular H2S-release mechanism requires the cooperation of reduced GSH, as elucidated by Kraus et al [13]. H2S represses programmed cell death and inflammation by downregulation of inflammatory cytokines, such as, for example, TNF-α, IL-1b, NF-kB, IL-8 and IL-6 [32,33,34,35]; it regulates blood pressure–lowering, and exerts anti-nociceptive and cardioprotective effects due to the activation of cardiac extracellular signal-dependent-kinases, such as Akt pathways and KATP channels [36,37]
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