人類胎盤間葉幹細胞具有自我更新及分化成脂肪、硬骨、軟骨等不同細胞系的潛能，因此可以做為再生醫學與組織工程的細胞來源。由於存在於體內的間葉幹細胞通常具有緩慢增殖的現象，因此在體外擴增培養時維持緩慢增殖的特性是保持間葉幹細胞處於前趨狀態最佳的方式。透明質酸是細胞外基質的一種，可以減緩細胞增殖速率。所以本研究將人類胎盤絨毛組織分離出的間葉幹細胞培養於濃度30μg/cm2 透明質酸塗附的介面上，藉由生長曲線觀測可以得到延緩細胞生長速率的現象，並且從飢餓處理36 小時後再回填10%血清以回復細胞週期的實驗中，我們可以利用PI 染色觀察到培養於30μg/cm2 透明質酸塗附介面上的間葉幹細胞中G0/G1 時期比在一般培養介面上延長18 小時。接著我們利用人類細胞週期cDNA晶片雜合做為偵測的工具，在透明質酸介面上培養的間葉幹細胞對於E2F4及CCND2 (cyclin D2)的基因表現，與一般介面有0.97 與1.01 比率的差異。再利用即時定量PCR 定量確認，人類胎盤絨毛間葉幹細胞培養在透明質酸介面，表現E2F4及CCND2 基因比一般介面上多出2.8 及5.9 倍。此外，我們利用西方免疫沉降和轉印的方法，證實在透明質酸介面下處於G0 休眠期及G1 期中的間葉幹細胞，會使得p27 的表現量上升造成CDK2 的活性下降而促使p130 上第986 位置的蘇胺酸磷酸化減少，因此將會導致E2F4 與p130 形成緊密的複合體存在，造成抑制或休止細胞週期；隨後，cyclin D2 表達量上升促使p27 磷酸化，並且從細胞核遞送到細胞質進行降解，使細胞週期得以進行。因此根據本研究中各項數據顯示，透明質酸可藉由p27影響CDK2 的活性下降造成p130 的累積以延長G0/G1 phase，同時也是維持人類胎盤絨毛間葉幹細胞緩慢生長的適當因子。藉由本論文的發現，使得透明質酸在調節間幹細胞生理周期的研究上更為了解，以促進其在再生醫學上的發展。

The mesenchymal stem cells from human placenta (PDMSC) have the characteristics of self-renewal and differentiation potentials of adipogenesis, osteogenesis, chondrogenesis,etc. They can be a good cell source for the future applications in regenerative medicine and tissue engineering.PDMSC have prolonged cell cycle in vivo; as a result in it was speculated that to maintain the properties of PDMSC ex vivo was to keep the cell in such
state. This research cultured PDMSC on surface coated with hyaluronan at a density of 30 μg/cm2 and on which the growth rate of cells was decreased.after starvation of 36 hours in serum-free medium and restoration of 10% bovine calf serum to the culture system, extension of G0/G1 phase in the cell cycle was observed to be 18 hours on the hyaluronan surface in comparison to regular cell culture surface.We then used cell cycle cDNA chip to detect gene expression and found that E2F4 and CCND2 (cyclin D2) were significantly up-regulated with a ratio difference of 0.97 and 1.01 in the hyaluronan group.And real-time PCR was used to confirm the result, and expression of E2F4 and CCND2 on hyaluronan coated surface was found to be 2.8 and 5.9 folds higher respectively than control group.Using immunoprecipitation and western blotting, we confirmed that G0 and G1 phase PDMSC cultured on hyaluronan coated surface would exhibit down-regulation of p27 which leads to supression of CDK2 activity and decreased phosphorylation of 986 threonine on p130, consequently E2F4-p130 complex forms thus G0/G1 phase is extended. Cell cycle proceeds when cyclin D2 is up-regulated which promotes phosphoryalation of p27.According to our data PDMSC cultured on surface coated with hyaluronan shows extended G0/G1 phase due to supression of CDK2 activity and accumulation of E2F4-P130 complex. So we speculate that hyaluronan coated on culture dish surface has the effect of maintaining PDMSC’s slow-cycling characteristic.

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