ABSTRACT
Cell therapy and tissue repair are used in a variety of diseases including tissue and organ transplantation, autoimmune diseases and cancers. Now mesenchymal stem cells (MSCs) are an attractive and promising source for cell-based therapy according to their individual characteristics. Soluble factors which are able to induce MSCs migration have a vital role in cell engraftment and tissue regeneration. Tumor necrosis factor α (TNF-α) is a major cytokine present in damaged tissues. We have investigated the pattern of gene expression of chemokine receptor CXCR4 in nine groups of human bone marrow-derived MSCs stimulated with TNF-α in different dose and time manner. Comparison of TNF-α treated with untreated MSCs revealed the highest expression level of CXCR4 after treatment with 1, and 10 ng/ml of TNF-α in 24 h, and the production of CXCR4 mRNA was regulated up to 216 and 512 fold, respectively. Our results demonstrated the differential gene expression pattern of chemokine receptor CXCR4 in human marrow-derived MSCs stimulated with inflammatory cytokine TNF-α. These findings suggest that in vitro control of both dose and time factors may be important in stem cell migration capacity, and perhaps in future-stem cell transplantation therapies.
Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Receptors, CXCR4/genetics , Tumor Necrosis Factor-alpha/metabolism , Bone Marrow Cells/cytology , Cell Movement , Cell Proliferation , Cells, Cultured , Gene Expression Regulation, Developmental , Humans , Mesenchymal Stem Cells/metabolism , Receptors, CXCR4/biosynthesis , Signal Transduction/genetics , Tumor Necrosis Factor-alpha/genetics , Wound HealingABSTRACT
Objectives: Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl4. Materials and Methods: CCl4 was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period. Results: CCl4 increased the level of malondialdehyde (P<0.01 in the kidney and P<0.001 in the testis) and nitric oxide (P<0.001 in the kidney and P<0.01 in the testis) and decreased the levels of glutathione (P<0.05) in the kidneys and testicles of rats. CCl4 also reduced the catalase enzyme activity in the kidneys (P<0.05) but did not affect its activity in the testis. In addition, CCl4 enhanced the mRNA expression of TNF-α (P<0.01), nuclear factor-κB (P<0.05), and Bax (P<0.05 in the kidney and P<0.01 in the testis) and decreased the expression of Bcl-2 (P<0.05) in both organs. Alpha-pinene prevented all the mentioned changes, but it did not influence the expression of Bcl-2 in the kidneys of rats receiving CCl4. Conclusion: Alpha-pinene may have the potential to prevent renal and testicular diseases by strengthening the antioxidant system in the kidneys and testis, and inhibiting oxidative/nitrosative stress, inflammation, and apoptosis caused by CCl4.