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 Â 10 6 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-a. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

Knockdown of mesenchymal stem cell‑derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway

“…MSCs have been demonstrated to be effective for the treatment of atherosclerosis, due to their ability to repair tissue, in addition to their anti-inflammatory and immunological properties ( 38 ). MSCs can be isolated from several types of tissues, including bone marrow, the umbilical cord, placenta, adipose tissue and human gingiva ( 39 , 40 ). MSCs that are used for the treatment of atherosclerotic plaques are primarily derived from the bone marrow ( 39 ), but can also be obtained the gingiva ( 41 ).…”

Correlation between stem cell molecular phenotype and atherosclerotic plaque neointima formation and analysis of stem cell signal pathways

“…At the same time, it has been shown in stem cell targeted therapy that bone marrow mesenchymal stem cells can replace damaged cells and promote neointima formation in atherosclerosis. This effect is worthy of recognition ( Hashem et al, 2021 ).…”