2011-10-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/689529摘要:本子計畫五將篩選具有維持人類間葉幹細胞(MSCs)自我更新能力的生醫材 料並研究其機制,之前我們已發現某些高分子材料會增加多潛能基因(Nanog, Oct4, Sox2)的表現,我們將使用微孔晶片篩選生醫材料,建立能促進幹細胞增生 與自我更新的高分子材料,並探討造成此一現象的機制;在瞭解這些機制的調控 後,我們將使用不同路徑之抑制劑探討其對分化可能造成之影響,並以裸鼠實驗 驗證之。另一方面,我們發現生醫高分子材料亦能增加細胞基因傳遞的效率,由 於MSCs基因傳遞的效率偏低,我們將利用此生醫材料策略將周邊神經再生相關 的神經滋養因子(如BDNF與GDNF)或促進心肌再生的因子(GATA4, MEF2C與 TBX5)傳遞到MSCs,並分別在周邊神經與心肌損傷之動物實驗證實能增加組織 再生<br> Abstract: Stem cells are considered as good cell sources for tissue engineering. Stem cells have the ability to renew themselves and to maintain their undifferentiated state. They could also differentiate into different specialized cell types when exposed to appropriate physical and chemical inductions. However, pluripotent stem cells can lose their stemness properties due to the in vitro culture environment. The transcription factors Oct4, Sox2, and Nanog that are important for the maintenance of the pluripotency of ESCs are also present in adult stem cells. Therefore, in this sub-project 5, we will use microwell chips to fast screen the biomaterials and identify those that can maintain the self-renewal of mesenchymal stem cells (MSCs), and explore the associated mechanisms for the increased self-renewal of MSCs on these biomaterials. We will also use different pathway inhibitors to promote certain differentiation on the biomaterials and test them in the nude mice model. Further, we will use biomaterials to enhance the efficiency of gene delivery and to transfect MSCs with a few genes [e.g. brain-derived neurotrophic factor (BDNF) and glia-derived neurotrophic factor (GDNF) genes that are supposed to increase the peripheral nerve regeneration; and on the other hand, GATA4, MEF2C, TBX5 that are supposed to increase the cardiomyogenesis]. Finally, we will test the efficacy of the transfected cells in the appropriate animal models in vivo.間葉幹細胞微孔晶片基因傳遞神經再生心肌再生mesenchymal stem cells (MSCs)microwell chipsgene delivery,幹細胞信息傳遞機制及臨床應用-生醫材料上幹細胞自我更新與基因傳遞--子計畫四(1/3)