Skin-Derived Mesenchymal Stem Cells Alleviate Atherosclerosis via Modulating Macrophage Function

Area of Science:

• Immunology
• Regenerative Medicine
• Cardiovascular Research

Background:

• Atherosclerosis (AS) is a chronic inflammatory disease characterized by plaque buildup.
• Mesenchymal stem cells (MSCs) show immunosuppressive properties.
• Skin-derived MSCs (S-MSCs) are an accessible source, but their role in AS is unclear.

Purpose of the Study:

• To investigate the therapeutic effect and mechanism of S-MSCs on atherosclerotic plaque formation in apolipoprotein E-knockout (apoE(-/-)) mice.
• To elucidate the role of nuclear factor-κB (NF-κB) signaling in S-MSC-mediated immunosuppression in AS.

Main Methods:

• Utilized apoE(-/-) mice model for atherosclerosis.
• Administered S-MSCs and NF-κB knockout S-MSCs.
• Assessed plaque size using ultrasound biomicroscopy and histological analysis.
• Investigated S-MSC migration to plaques and interaction with macrophages.
• Conducted in vitro co-culture experiments with macrophages and S-MSCs stimulated by lipopolysaccharide (LPS).

Main Results:

• S-MSC treatment significantly reduced atherosclerotic lesion size and plaque area in apoE(-/-) mice.
• S-MSCs migrated to atherosclerotic plaques and interacted with macrophages.
• S-MSC treatment decreased pro-inflammatory tumor necrosis factor-alpha (TNF-α) and increased anti-inflammatory interleukin-10 (IL-10) in plaques, dependent on NF-κB.
• In vitro, S-MSCs promoted prostaglandin E2 (PGE2) release, which enhanced IL-10 production by macrophages and reduced TNF-α/IL-1β, mediated via EP2/EP4 receptors and NF-κB signaling.

Conclusions:

• S-MSCs attenuate atherosclerosis plaque formation by modulating macrophage function.
• The mechanism involves PGE2-mediated signaling, leading to reduced inflammation and increased anti-inflammation.
• S-MSC efficacy is dependent on NF-κB signaling.
• S-MSCs represent a promising cell source for stem cell-based therapy for atherosclerosis.