基質硬度影響角膜表皮細胞在電場中之遷移

Abstract

細胞遷移出現在許多生理現象，例如傷口癒合，腫瘤細胞的轉移，器官發育，免疫反應以及人體形態上的變化。影響細胞遷移有許多因素，包括電場，基質的軟硬度，以及周遭化學物質的濃度。羊膜常常被用來治療角膜持久不癒合的表皮層缺損。為了瞭解羊膜能夠幫助傷口癒合的機轉，我們使用牛的角膜表皮細胞，用外加電場來模擬傷口上的內生電場，以各種不同的基質觀察細胞在其上的遷移現象。我們發現在羊膜及角膜的基底膜，以及低濃度的膠原蛋白上可以得到最快的遷移速度以及最好的方向性。第一型及第四型膠原蛋白的影響大於纖維結合蛋白和基膜粘連蛋白。此時多數細胞呈現紡錘狀並且產生較多細胞遷移時出現的偽足。我們進一步利用不同軟硬度的海藻膠來研究細胞遷移，發現細胞確實受基質的機械性質所影響，細胞偏好在較硬的基質上移動。因此當我們考慮促進傷口癒合的同時，基質表面的物理性質是一項重要的考量。本篇研究有助於了解傷口癒合的機制以及作為治療上的參考。

Cell migration involves in many fields, such as wound healing, tumor metastasis, organ development, immune response and morphological change. Cell migration is affected by many factors, such as electric field, rigidity of the substrate, and chemical gradient. Amniotic membrane (AM) is commonly used to treat persistent corneal injuries. In an attempt to understand mechanisms behind this enhancement of the healing process, bovine corneal epithelial cells were used to examine cell migration on the various substrates. External electric field was applied to simulate the intrinsic current generated at corneal wound edges. Higher migration speed and directional velocity were found on the basement membrane side of AM, cornea section and on lower collagen concentrations. Collagen type I and type IV both benefit cell migration rather than fibronectin and laminin. At the same time, most cells assume a spindle shape and form more lamellipodia in these conditions that may correspond with the migration result. The studies on calcium alginate with varied stiffness prove that cell responses to differential mechanical forces between cell and substrate, and cells prefer to migrate on maximal mechanical input. When enhancing wound healing with any substrate, the physical properties of surface is always something to be considered. Result from this study may benefit our understanding of the cornea wound healing mechanism and provide further treatment options.