力學與化學機轉調節內皮細胞隨機形成體外初期微血管叢之建模與模擬

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姓名

姜洵(CHIANG, HSUN) 查詢紙本館藏

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機械工程學系

論文名稱

力學與化學機轉調節內皮細胞隨機形成體外初期微血管叢之建模與模擬

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摘要(中)

體外培養內皮細胞形成微血管網絡結構，是組織工程領域中一項日趨重要的議題。經由先前學者的相關研究發現，已知促使內皮細胞聚集形成微血管之機制可能有二：其ㄧ為細胞與細胞外基質之間的受力平衡關係，其二則為在培養環境中血管內皮生長因子的濃度變化。本研究建立了同時包含此兩種機制之數學模型，在模型中以離散之細胞帕茲模型描述內皮細胞的個體遷移行為，而對於細胞外基質的變形以及血管內皮生長因子的濃度分布則以連續體模型進行定量分析。以此模型計算後得到之內皮細胞分布形態與實驗數據相符，證明內皮細胞形成微血管網絡結構之過程，確實為力學與化學機制共同作用下所產生的結果，並且藉由調整模型中之各項參數值進行數值模擬分析，推論得知此兩種機制於細胞、基質、以及血管內皮生長因子三者之間的交互作用關係為：內皮細胞之牽引力使基質材料產生密度變化後，將間接造成血管內皮生長因子在空間中的不均勻分布，其後內皮細胞將因趨觸性影響而於血管內皮生長因子之濃度較高處聚集，最終發展為穩定之微血管網絡結構。

摘要(英)

How the endothelial cells forming capillary networks is an important issue that has not been completely addressed in tissue engineering. Studies have showed that there might be two mechanisms underlying the network patterning: the mechanical force balance between cells and extracellular matrix, and the chemical attraction by VEGF in the surroundings. This study proposes a mathematical model that considers both the mechanical and chemical mechanisms. The stochastic behavior of cell migration is described using the cellular Potts model, and the biogel and chemical attractant VEGF are treated as continua in modeling the biogel displacement and VEGF distribution. Results from the simulation agree well with previous experimental data, showing that endothelial cells can form capillary-like structures only when both the mechanical and chemical mechanisms work together. The interaction between cells, biogel and VEGF could also be inferenced from the parametric analysis. That is, once the cells impair the uniform distribution of biogel, the VEGF gradients form as well since VEGF is binding with biogel molecules, thus the endothelial cells migrate and gather via haptotaxis. Finally, the cells, biogel and bound VEGF will accumulate at some local locations and form the stable in vitro plexus.

關鍵字(中)

★ 內皮細胞
★ 網絡結構
★ 細胞牽引力
★ 血管內皮生長因子
★ 細胞帕茲模型

關鍵字(英)

論文目次

中文摘要 i
Abstract ii
目錄 iii
表目錄 v
圖目錄 vi
符號表 viii
第一章緒論 1
1.1. 研究動機 1
1.2. 文獻回顧 2
1.2.1 微血管的形成與培養 2
1.2.2 描述微血管形成過程的數學模型 4
1.3. 研究目的 5
1.4. 研究方法 6
1.5. 論文架構 7
第二章數學模型 10
2.1. 問題描述 10
2.2. 統御方程式 11
2.2.1 細胞方程式－細胞帕茲模型 11
2.2.2 細胞外基質方程式 15
2.2.3 血管內皮生長因子方程式 18
2.3. 初始條件 19
2.4. 邊界條件 20
2.5. 無因次化 21
2.6. 數值方法 24
2.6.1 計算流程 24
2.6.2 軟體簡介 25
2.6.3 MATLAB 之相關設置 26
2.6.4 COMSOL Multiphysics 之相關設置 27
第三章　模擬結果與實驗比對 36
3.1. 細胞網絡結構的形成過程 36
3.2. 細胞外基質厚度對網絡結構的影響 40
3.3. 血管內皮生長因子對網絡結構的影響 41
第四章參數分析 61
4.1. 內皮細胞的遷徙特性 61
4.1.1 細胞擴散性強度對網絡結構的影響 61
4.1.2 細胞移流性強度對網絡結構的影響 62
4.1.3 細胞趨觸性強度對網絡結構的影響 63
4.2. 細胞與細胞外基質的交互作用 64
4.2.1 細胞對基質施加之牽引力強度對網絡結構的影響 64
4.2.2 細胞對基質上貼附點之競爭現象對網絡結構的影響 65
4.3. 細胞外基質與血管內皮生長因子的交互作用 66
4.3.1 血管內皮生長因子與基質分子之結合率對網絡結構的影響 66
4.3.2 血管內皮生長因子與基質分子之分離率對網絡結構的影響 67
第五章結論與未來展望 86
參考文獻 89

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吳思穎，2012，體外培養內皮細胞形成毛細血管結構前期之穩定性分析及模擬，國立中央大學碩士論文。

指導教授

鍾志昂

審核日期

2017-8-14

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