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研究生:洪也婷
研究生(外文):Hung-Yeh Ting
論文名稱:人類多能力的基質細胞調整培養基經由介白質6促進傷口癒合
論文名稱(外文):Interleukin-6 mediates wound healing enhanced by human multipotent stromal cell conditioned medium
指導教授:洪士杰
指導教授(外文):Shih-Chieh Hung
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:34
中文關鍵詞:介白質6人類間葉幹細胞調整培養基細胞移動傷口癒合內皮細胞上皮細胞
外文關鍵詞:IL-6conditioned mediumcell migrationwound healingendothelial cellsepithelial cells
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一些文章指出,慢性傷口的癒合處理效果有限,但可經由移殖骨髓間葉幹細胞改善此情形。我們假設骨髓間葉幹細胞是經由分泌效果來促進傷口癒合,所以我們測試人類間葉幹細胞調整培養基的效果情形。藉由使用動物傷口模式,結果顯示人類間葉幹細胞調整培養基注射在傷口周圍及敷在傷口上和對照組一般培養基比起來可以明顯促進傷口癒合。這個癒合過程是經由增加上皮細胞再生、細胞浸潤、肉芽形成及血管新生。值得注意的是人類間葉幹細胞調整培養基可以促進上皮細胞及血管內皮細胞移動,這表示傷口癒合過程中促進細胞移動的效果是來自於人類間葉幹細胞調整培養基。有些研究指出介白質6能夠刺激血管內皮細胞增生、移動以及matrigel管形成,此刺激和介白質6劑量成正相關;而抗介白質6抗體或是接受體可以阻斷這個效果。因為間葉幹細胞是藉由分泌來促進傷口癒合而介白質6可能在其中扮演重要角色。利用細胞漿檢測在間葉幹細胞調整培養基中也分析出含高量的介白質6。定量RT-PCR也可檢測出在間葉幹細胞有介白質6的表現。除此之外,在一般培養基加入介白質6能夠促進細胞移動和傷口癒合,而抗介白質6抗體能夠阻斷此促進效果。間葉幹細胞分泌介白質6的途徑可被p38 MAPK抑制劑 SB203580阻斷或被對於p38 MAPK的siRNA阻斷,這表示間葉幹細胞分泌介白質6是經由p38 MAPK的持續活化。所以,我們的結果顯示間葉幹細胞藉由分泌介白質6來促進傷口癒合,而且間葉幹細胞調整培養基也許可以應用在促進傷口癒合上。
Although treatment of chronic wounds remains limited and often ineffective, it can be improved through bone marrow-derived mesenchymal stem cell (MSC) transplantation. We hypothesized that MSC-enhanced wound healing was partly due to paracrine effects. Thus, we examined the effects of conditioned medium derived from a human MSC culture (CM-MSC) in wound healing. Using an excisional wound splinting model, we observed that CM-MSC significantly enhanced wound healing in mice as compared with the control preconditioned medium after direct application to the wound and wound bed. CM-MSC-treated wounds displayed significantly accelerated wound closure, with increased reepithelialization, cell infiltration, granulation formation, and angiogenesis. Notably, CM-MSC but not preconditioned medium enhanced epithelial and endothelial cell migration, highlighting the contribution of increased cell migration enhanced by CM-MSC during wound healing. Previous reports have demonstrated that interleukin- 6 (IL-6) stimulates endothelial cell proliferation, migration, and matrigel tube formation in a dose-dependent manner; application of anti-IL-6 blocking antibodies or IL-6 receptor abolished these effects. Because MSCs promote wound healing through secretion of a paracrine factor, IL-6 expression and secretion were analyzed. Cytokine array and enzyme-linked immunosorbent assay (ELISA) analysis of CM-MSC revealed high levels of IL-6. In addition, quantitative RT-PCR revealed expression of IL-6 in MSCs. Moreover, addition of IL-6 to the preconditioned medium enhanced both cell migration and wound healing, and antibodies against IL-6 blocked the enhanced cell motility and wound closure induced by CM-MSC. Inhibition of IL-6 secretion was observed using SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), or p38 MAPK siRNA, suggesting that IL-6 secretion by MSCs is mediated through the constitutive activation of p38 MAPK. Thus, our data suggest that MSCs promote wound healing through IL-6 secretion, and application of CM-MSC may be useful for enhancing wound healing.
Table of ContentsChinese Abstract     1English Abstract     2-3List of Abbreviation     4-5Introduction     6-7Material and Methods     8-14Results     15-18Discussion     19-20Conclusions and Prospects     21-22References     23-27Figures and Legends    28-34
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