Activation of liver X receptor improves viability of adipose-derived mesenchymal stem cells to attenuate myocardial ischemia injury through TLR4/NF-κB and Keap-1/Nrf-2 signaling pathways.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Aims Clinical application of cellular therapy for cardiac regeneration is significantly hampered by the low retention of engrafted cells, mainly attributable to the poor microenvironment dominated by inflammation and oxidative stress in the host's infarcted myocardium. This study aims at investigating whether liver X receptor (LXR) agonist T0901317 will improve survival of adipose-derived mesenchymal stem cells (AD-MSCs) after transplantation into infarcted hearts. Results Noninvasive in vivo bioluminescence imaging and histological staining showed that LXR agonist T0901317 improved the retention and survival of intramyocardially injected AD-MSCs. Moreover, combined therapy of LXR agonist and AD-MSCs inhibited host cardiomyocyte apoptosis, reduced fibrosis, and improved cardiac function, while it concomitantly decreased inflammatory cytokines (e.g., tumor necrosis factor-α and interleukin-6) and increased growth factor (e.g., vascular endothelial growth factor and basic fibroblast growth factor) expression in infarct myocardium. To reveal possible mechanisms, AD-MSCs were subjected to hypoxia/serum deprivation (H/SD) injury to simulate ischemic conditions in vivo. The LXR agonist (10(-7) mM) improved AD-MSC survival under H/SD condition. Western blot revealed that the LXR agonist reduced TLR4, TRAF-6, and MyD88 protein expression, inhibited IκBα phosphorylation and NF-κB-p65 nu

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.