| 研究生: |
阮得幸孝 Hieu, Nguyen Dac Hanh |
|---|---|
| 論文名稱: |
透明質酸於胎盤間葉幹細胞在休眠及增生切換之作用機轉 The switching mechanism between quiescence and proliferation of PDMSC affected by hyaluronan |
| 指導教授: |
黃玲惠
Huang, Ling-Huei |
| 學位類別: |
碩士 Master |
| 系所名稱: |
生物科學與科技學院 - 生物科技與產業科學系 Department of Biotechnology and Bioindustry Sciences |
| 論文出版年: | 2020 |
| 畢業學年度: | 108 |
| 語文別: | 英文 |
| 論文頁數: | 105 |
| 中文關鍵詞: | 幹細胞 、透明質酸 、胞外基質 、靜止 、增生 、蛋白質組學。 |
| 外文關鍵詞: | stem cell, hyaluronan, extracellular matrix, quiescence, proliferation, proteomics. |
| 相關次數: | 點閱:103 下載:2 |
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間充質幹細胞(MSCs)在臨床應用中是最有潛力的多功能幹細胞由於他的分化能力。MSC常受到所在的利基影響,其中透明質酸(HA)是細胞外基質(ECM)重要組成分也是幹細胞常存在之利基。在過去研究顯示,HA塗佈在培養皿上培養細胞會使細胞的生長變慢,然而HA如何調控幹細胞休眠及增生機制還不是很清楚。而在本研究中,胎盤間葉幹細胞(PDMSC)分別在三種不同條件下進行培養:濃度30 µg / cm2的HA塗佈在培養皿(CHA30)、含濃度1 µg / ml的HA懸浮液(SHA1)的培養皿及未處理HA的培養皿(TCS)。結果顯示,CHA30有高分子量之HA,會降低PDMSC生長速率;然而SHA則會加速PDMSC生長速率,但不同SHA分子量之HA生長卻沒有顯著差異。再者,流式細胞儀分析的數據表示,與SHA1相比,CHA30延長了G0期的PDMSC。這項研究對於以HA調控PDMSC靜止和增殖相關的蛋白質和基因具有完整的研究。 JAK / STAT、PI3K / Akt和Ras / Map信號是已知調節細胞增殖的路徑,在SHA1和CHA30轉換SHA1(CS)中被上調,而TGF-β和p53途徑中在CHA30和SHA1轉換CHA30(SC)中的表現明顯更高。 因此,在研究發現有力地證明了HA在上述這些路徑對PDMSC增殖和靜止之間切換是重要的。此外,也為透明質酸的應用開闢了新的視野,特別是透明質酸與間充質幹細胞生物學相關機制奠定了基礎。
Mesenchymal stem cells (MSCs) are one of the most promising multipotent cells due to their potential in clinical application. The value of MSCs is directly related to the stem cell niche where they original belongs. Hyaluronan (HA) is a crucial extracellular matrix (ECM), is always found in the stem cell niche. Previous studies demonstrated that HA affects the stem cell proliferation rate. However, the mechanism by which HA can switch stem cells between quiescence and proliferation still a mystery. In this report, placenta-derived mesenchymal stem cells (PDMSC) was cultured under three different conditions as follows: HA-coated at a concentration of 30 µg/cm2 (CHA30), HA-suspension at a concentration of 1 µg/ml (SHA1), and without treatment of HA as tissue culture surface (TCS). Initially, CHA30 has been shown the higher molecular weight of HA, the slower in the growth rate of PDMSC proliferation, whereas SHA1 demonstrated in promoting cell proliferation and no significant differences in cell growth curve in terms of different molecular weight. Furthermore, the data from flow cytometry analysis suggested that CHA30 prolonged PDMSC in G0 phase compared to SHA1. This study has a complete in researching the protein and genes associated with quiescence and proliferation in PDMSC under the HA treatment. The JAK/STAT, PI3K/Akt, and Ras/Map signaling which are well-known pathways in regulating cell proliferation, are up-regulated in SHA1 and CHA30 switched SHA1 (CS), whereas the TGF-β and p53 pathway have been shown significantly higher in the expression in CHA30 and SHA1 switched CHA30 (SC). Hence, the promising reveal at the end of this study strongly demonstrates those pathways are essential in switching PDMSC between proliferation and quiescence. In addition, it opens a new horizon in HA application, in particular, the foundation of the mechanisms related to the biological process of mesenchymal stem cells by hyaluronan.
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