Biological effects of melatonin on human adipose‑derived mesenchymal stem cells

Abstract

Mesenchymal stem cells (MScs) are capable of differentiating into other cell types and exhibit immunomodulatory effects. MScs are affected by several intrinsic and extrinsic signaling modulators, including growth factors, cytokines, extracellular matrix and hormones. Melatonin, produced by the pineal gland, is a hormone that regulates sleep cycles. Recent studies have shown that melatonin improves the therapeutic effects of stem cells. The present study aimed to investigate whether melatonin enhances the biological activities of human adipose-derived MScs. The results demonstrated that treatment with melatonin promoted cell proliferation by inducing SRY-box transcription factor 2 gene expression and preventing replicative senescence. In addition, melatonin exerted anti-adipogenic effects on MScs. PcR analysis revealed that the expression of the ccAAT enhancer binding protein a gene, a key transcription factor in adipogenesis, was decreased following melatonin treatment, resulting in reduced adipogenic differentiation in an in vitro assay. The present study also examined the effect of melatonin on the immunomodulatory response using a co-culture system of human peripheral blood mononuclear cells and MScs. Activated T cells were strongly inhibited following melatonin exposure compared with those in the control group. Finally, the favorable effects of melatonin on MSCs were confirmed using luzindole, a selective melatonin receptor antagonist. The proliferation-promoting, anti-inflammatory effects of melatonin suggested that melatonin-treated MScs may be used for effective cell therapy.

Exosome and Melatonin Additively Attenuates Inflammation by Transferring miR-34a, miR-124, and miR-135b

“…At varying concentrations, 10 μ M of melatonin resulted in the highest growth rate after 3 d of culture ( Figure 4(a) ). These results are in line with those of a previous study [ 15 ]. Therefore, melatonin at 10 μ M was used as the optimal concentration.…”

Melatonin Promotes the Proliferation of Chicken Sertoli Cells by Activating the ERK/Inhibin Alpha Subunit Signaling Pathway

“…For example, melatonin has a proliferative effect in a variety of cells and in mouse spermatogonia, melatonin not only promotes cell proliferation by the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, but also by increasing metallothionein 2 (Mt2) [29]. In mesenchymal stem cells, melatonin promotes cell proliferation by inducing expression of the SRY-box transcription factor 2 gene and preventing replicative senescence [30]. Similarly, a melatonin treatment of neural stem cells in hypoxia is a powerful strategy which could increase cell proliferation and reduce cell death [31].…”

Melatonin potentials against viral infections including COVID-19: Current evidence and new findings

“…Melatonin is reported to reduce inflammatory responses through the management of pro-inflammatory cytokines such as interleukin 1 beta (IL-1β), TNF-α, and IL‑6. Furthermore, melatonin treatment could efficiently attenuate T cell proliferation in association with the down-regulation of IL‑6 and IL‑10 expression ( Heo et al, 2019 ).…”