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Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM).

ABSTRACT: Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34+ stem cells (6×106 cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

SUBMITTER: Hashem RM

PROVIDER: S-EPMC8148879 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background：Atherosclerosis is the major cause of cardiovascular disease. Endothelial injury is one of the initiating factors of atherosclerosis. Injured endothelial cells overexpress adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), facilitating the binding and accumulation of monocytes-macrophages into the vascular wall via the ligands. Adipose-derived stem cells (ADSCs) have been extensively researched for their anti-inflammatory properties and therapeutic potential in various diseases. Targeting atherosclerotic regions with ADSCs may offer a promising therapeutic strategy to alleviate local inflammation associated with atherosclerosis.Methods：The ligands of very late antigen-4 (VLA-4) and lymphocyte function-associated antigen-1 (LFA-1) were expressed in the ADSC to construct the Macrophage (Mφ)-mimicking ADSCs. Cell proliferation, adhesion, and migration assays were used to characterize the Mφ-mimicking ADSCs. An atherosclerosis model was established in ApoE-/- mice via partial carotid artery ligation. Mφ-mimicking ADSCs were administered through tail vein injection. Distribution of these cells was tracked by far-red fluorescent probe. Histological analyses, including H&E staining, Oil Red O staining, and immunofluorescence were conducted to assess the impact on plaque size, composition, and macrophage polarization.Results：Mφ-mimicking ADSCs were successfully constructed and characterized. These cells exhibited enhanced adhesion and migration capabilities. The culture medium from Mφ-mimicking ADSCs increased the proportion of M2 macrophages and decreased the lipid uptake capacity. In the atherosclerosis mouse model, fluorescently labeled Mφ-mimicking ADSCs specifically adhered to and accumulated in atherosclerotic regions, demonstrating targeted localization. Mφ-mimicking ADSC treatment resulted in a reduction in plaque size and a decrease in the number of M1 macrophages within the arterial wall.Conclusions：Mφ-mimicking ADSCs confirmed their preserved anti-inflammatory properties and enhanced adhesion and migration abilities. In vivo, Mφ-mimicking ADSCs exhibited targeted localization ability to regions of endothelial dysfunction in atherosclerosis and attenuate plaque progression. These findings suggest that Mφ-mimicking ADSCs may serve as a potential therapeutic strategy for alleviating atherosclerosis and reducing inflammation.

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Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM).

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