Study on the Mechanism of Immune Regulation and Inflammation in the Differentiation of Mesenchymal Stem Cells

• Main Authors: Min-Jyun Fan-Jiang, 范姜旻君
• Other Authors: 江伯倫
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/56108202053274027235

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 102 === Mesenchymal stem cells (MSCs) are self-renewable multipotent progenitor cells that have the potential to differentiate into various of cell types including adipocytes, osteocytes and chondrocytes. Recent studies have demonstrated that MSCs could exert an immunosuppressive activity. However, many obesity-related metabolic diseases such as type II diabetes are attributed to adipocyte-induced inflammation. And macrophages were recruited by adipose tissue-derived hormones or chemokines, may play the key roles on the chronic inflammation. We hypothesized that some mediators might be changed during the adipogenesis processes of MSCs. Hence, this study was performed to examine the gene and cytokine profiles of MSCs in different differential processes. First, MSCs were isolated from mouse bone marrow, characterized by their phenotypes, and differentiated into adipocytes, osteocyte and chondrocytes in the appropriate induction media. In addition, the immunosuppressive function of MSCs was determined in vitro by T cell proliferation assay. After IFN-γ and TNF-α induction, high expression of iNOS, COX-2, IL-1RA and IL-6 in MSCs but low expression in 3T3-L1 adipocytes were noted. However, MCP-1 and TNF-α were expressed in 3T3-L1 adipocytes but not MSCs. When IFN-γ and TNF-α were given to three different differential processes of MSCs, respectively, the expression of IL-1RA was negative correlated with adipogenesis progress of MSCs. Peroxisone proliferator-activated receptors (PPARs) can promote adipogenesis by inhibiting IL-1RA expression through NF-κB signaling pathway. The results indicated that PPARs involved in IL-1RA regulation was also involved in adipogenesis of MSCs by the use of PPRAs antagonist and PPARs agonist. This research provides rational mechanisms supporting the clinical application of allogeneic MSCs.