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.
Subject(s)
Animals , Rats , Vascular Cell Adhesion Molecule-1 , Atherosclerosis/therapy , Cell Adhesion , Intercellular Adhesion Molecule-1 , Myocytes, Smooth Muscle , Cell- and Tissue-Based TherapyABSTRACT
To investigate the mechanisms of the rarity of metastasis to skeletal muscles. Animal models of blood borne metastasis to skeletal muscle and lung were established,VCAM 1 expressions of the microvascular endothelium in these organs were estimated using immunohistochemistry.The effects of skeletal muscle conditioned media(MCM) on several tumor cell lines were tested by MTT assay.Tumor cells or metastatic foci could be seen rarely in the connective tissue beside muscle bundles of the femoral muscles,however, there is no metastatic foci among muscle cells.The difference of metastatic rate between skeletal muscles and lungs was significant( P