流體剪力在ㄧ特定細胞的微環境中給予適當的刺激，以調節機械力傳導維持細胞功能，包括生理平衡、細胞形態學以及移動性。當不適當的流體剪力刺激時則會導致此細胞喪失功能性而促進疾病發展，例如增加流體剪力於腎上皮細胞會導致多囊性腎臟和在靜脈移植手術的靜脈內皮細胞（EC）功能受損。然而，細胞是如何感受流體剪力刺激進而影響細胞功能與機制仍尚未明了。因此假設在不同微環境下適當流體剪力對特定細胞時能促進與維持細胞功能。本研究將分為兩個目的從腎臟組織工程到血管病理學中探討對細胞反應的影響。首先：探討適當的流體剪力對腎小管上皮細胞於組織工程中角色，其結果發現腎臟上皮細胞（MDCK）的形態可藉由與膠原蛋白包覆的脂肪細胞幹細胞（ASCs）共培養增加了細胞高度，其具有柱狀形態，纖毛形成和離子轉運蛋白的功能表達。當施加低流體剪力（0.5 dyne/cm2）在以轉染GFP-微管蛋白的MDCK上，會促進表達GFP-微管蛋白中纖毛的形成，並在此微環境可防止細胞在微流體系統的長期細胞共培養中死亡。論文的第二部分闡述了動脈流體剪力（ALS，12 dyne/cm2）對動脈和靜脈EC的影響。我們發現ALS誘導動脈ECs有細長形態，其細胞型態方向性平行於流體方向。相反，靜脈內皮細胞在ALS發作後會引發脫落。在轉染GFP-黏著蛋白酶（GFP-FAK）的ECs中，ALS會增快動脈FAK dynamic，而減慢靜脈ECs的FAK dynamic。ALS也未能活化靜脈EC的Src和消退極化現象。有趣的是，上皮生長因子（EGF）可促進靜脈ECs 的FAK dynamic和極化Src來防止靜脈內皮細胞的損失和脫落。其結果表示當給予不適當的高流體剪力微環境會引發靜脈內皮細胞FAK-Src的時空差異而導致細胞丟失。因此，本篇研究發現低流體剪力有助於腎上皮細胞功能化;高流體剪力促進動脈ECs功能而引起靜脈ECs受損。表示微環境中提供適當流體剪力於不同細胞類型會促進細胞功能，而維持細胞生理機制以防止組織病理學進展具有重要意義。

The proper shear stress in the microenvironment of a specific cell type can modulate mechanotransduction to maintain cellular functions including homeostasis, mobility, and morphology. Improper shear stress results in the disease progressions. For example, the abnormal shear stress in the renal epithelial cells leads to polycystic kidney disease and endothelial cells (EC) dysfunction in patients with vein graft surgery. Hence, we hypothesized that different intensity of shear stress influences varied responses of cell function. This study has two purposes: proper shear stress is important for kidney tubule tissue engineering and the identities and characteristics of arterial and venous EC. First, in kidney tissue regeneration, the morphology of madin-darby canine kidney (MDCK) increased cell height with columnar shapes, cilia formation and the functional expression of the ion transport protein by co-culture of adipocyte stem cells (ASCs) encapsulated with collagen gel (CG-ASCs) as compared without ASCs under static condition. Renal shear stress of 0.5 dynes/cm2 is applied to MDCK facilitated the improvement of cilia formation in the GFP-tubulin expressing MDCK and create a microenvironment to prevent cells death in long-term cell coculture from microfluidic system. The second part of the thesis illustrated the impacts of arterial laminar shear stress (ALS, dynes/cm2) on arterial and venous EC (vEC). vEC showed smaller FA size and higher FA number with prolonged FAK assembly/disassembly under ALS. ALS-induced spatial activations of FRET-Src at cellular upstream region were also disappeared in vEC. Inhibiting FAK in arterial cells abolished the ALS-induced FA dynamics and resulted to vEC phenotype for cell peel-off. Instead, rescue FA dynamics in vEC by treating epithelial growth factor activated Src and FAK to prevent the loss of vEC. In conclusion, Renal shear stress assists functionalized renal epithelial cell; arterial shear stress acts benefit effect on arterial ECs, not on vEC. The results implied the shear stress of microenvironment in different cell types has the different effect that is important for maintaining cell physiologic functions to prevent the progression of tissue pathology.

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