期刊
BIOMATERIALS
卷 32, 期 34, 页码 8830-8838出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.08.006
关键词
Cell sheet; Cell alignment; Collagen; Micropatterning; Tissue engineering; Thermoresponsive surface
资金
- New Energy Industrial Technology Development Organization (NEDO), Japan
- Formation of Innovation Center for Fusion of Advanced Science and Technologies in the Special Coordination Funds for Promoting Science and Technology Cell Sheet Tissue Engineering Center (CSTEC)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [20300169]
- Grants-in-Aid for Scientific Research [20300169] Funding Source: KAKEN
Normal human dermal fibroblasts were aligned on micropatterned thermoresponsive surfaces simply by one-pot cell seeding. After they proliferated with maintaining their orientation, anisotropic cell sheets were harvested by reducing temperature to 20 degrees C. Surprisingly, the cell sheets showed different shrinking rates between vertical and parallel sides of the cell alignment (aspect ratio: approx. 3: 1), because actin fibers in the cell sheets were oriented with the same direction. The control of cell alignment provided not only a physical anisotropy but also biological impacts to the cell sheet. Vascular endothelial growth factor (VEGF) secreted by aligned fibroblasts was increased significantly, whereas transforming growth factor-beta 1 (TGF-beta 1) expression was the same level in anisotropic cell sheets as cell sheets having random cell orientations. Furthermore, although the amount of deposited type I collagen was different non-significantly onto between cell sheets with and without controlled cell alignment, collagen deposited onto fibroblasts sheets with cell alignment also showed anisotropy, verified by a fluorescence imaging analysis. The physical and biological anisotropies of cell sheets were potentially useful to construct biomimetic tissues that were organized by aligned cells and/or extracellular matrix (ECM) including collagen in cell sheet-based regenerative medicine. Furthermore, due to the unique thermoresponsive property, the anisotropic cell sheets were successfully manipulated using a gelatin-coated plunger and were layered with maintaining their cell alignment. The combined use of the anisotropic cell sheet and cell sheet manipulation technique promises to create complex tissue that requires the three-dimensional control of their anisotropies, as one of the next-generation cell sheet technologies. (C) 2011 Elsevier Ltd. All rights reserved.
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