Melatonin facilitates adipose‐derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway

Abstract

Mesenchymal stem cells (MSCs)-based therapy provides a promising therapy for the ischemic heart disease (IHD). However, engrafted MSCs are subjected to acute cell death in the ischemic microenvironment, characterized by excessive inflammation and oxidative stress in the host's infarcted myocardium. Melatonin, an indole, which is produced by many organs including pineal gland, has been shown to protect bone marrow MSCs against apoptosis although the mechanism of action remains elusive. Using a murine model of myocardial infarction (MI), this study was designed to evaluate the impact of melatonin on adipose-derived mesenchymal stem cells (AD-MSCs)-based therapy for MI and the underlying mechanism involved with a focus on silent information regulator 1(SIRT1) signaling. Our results demonstrated that melatonin promoted functional survival of AD-MSCs in infarcted heart and provoked a synergetic effect with AD-MSCs to restore heart function. This in vivo effect of melatonin was associated with alleviated inflammation, apoptosis, and oxidative stress in infarcted heart. In vitro studies revealed that melatonin exert cytoprotective effects on AD-MSCs against hypoxia/serum deprivation (H/SD) injury via attenuating inflammation, apoptosis, and oxidative stress. Mechanistically, melatonin enhanced SIRT1 signaling, which was accompanied with the increased expression of anti-apoptotic protein Bcl2, and decreased the expression of Ac-FoxO1, Ac-p53, Ac-NF-ΚB, and Bax. Taken together, our findings indicated that melatonin facilitated AD-MSCs-based therapy in MI, possibly through promoting survival of AD-MSCs via SIRT1 signaling. Our data support the promise of melatonin as a novel strategy to improve MSC-based therapy for IHD, possibly through SIRT1 signaling evocation.

Embryonic stem‐like cells from rabbit blastocysts cultured with melatonin could differentiate into three germ layers in vitro and in vivo

“…Recent research has pointed to the beneficial effect of melatonin on promoting embryo development and inhibiting apoptosis (Do et al, ; Han et al, ; Su et al, ). Our data extend these benefits to ESCs: supplementing 10 −7 M melatonin into the basic culture medium significantly facilitated primary ICM proliferation and rES‐like cells passaging, and enriched for the expression of some pluripotent genes compared to controls.…”

Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation

“…HUVECs were grouped into four experimental groups: Young, Young + Leo (10 μmol/L), Senescent, Senescent + Leo (10 μmol/L). HUVECs were stimulated with hypoxia to mimic in vivo ischemia as described previously (Han et al, 2016). All experimental groups were maintained in a hypoxic chamber (37°C, with 94% N 2 , 1% O 2 , and 5% CO 2 ) (Thermo Fisher Scientific, Waltham, MA, United States) for different periods, and leonurine was added 30 min before hypoxia.…”

Dietary Sources and Bioactivities of Melatonin

“…Melatonin was proved to increase the survival of adipose-derived mesenchymal stem cells in infarcted heart in mice at 20 mg/kg by activating SIRT1 signaling [256]. Besides, melatonin was found to significantly reduce the infarct size in myocardial ischemia-reperfusion injury (IRI) and decrease apoptosis through the activation of Janus kinase 2 (JAK2)/STAT3 signaling and PI3K/Akt signaling [257,258].…”