Development of Three-Dimensional Biomimetic Scaffold to Study Epithelial-Mesenchymal Interactions
Development of Three-Dimensional Biomimetic Scaffold to Study Epithelial-Mesenchymal Interactions
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DOI：
10.1089/ten.tea.2009.0110
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发表时间：
2010-01-01
影响因子：
4.1
通讯作者：
George, Anne
中科院分区：
文献类型：
--
作者：
Ravindran, Sriram;Song, Yiqiang;George, Anne
上皮-间充质相互作用在牙齿、肺和肾脏等组织的发育中起着关键作用。为了成功地设计或修复这样的活组织，有必要首先了解器官发生背后复杂的细胞-细胞和细胞-基质相互作用。为了模拟体内环境，有必要组装三维基质，以促进细胞间相互作用，导致细胞增殖和细胞分化。在这项研究中，我们开发了一个体外三维多层共培养系统，以I型胶原蛋白和壳聚糖混合物为基质，研究牙齿形态发生过程中上皮-间质相互作用。本研究结果表明，基质组成影响上皮细胞和间充质细胞的迁移、增殖和分化特性。具体来说，该系统支持HAT-7上皮细胞和间充质来源的牙髓干细胞的迁移和分化。共培养系统在小鼠体内的植入研究结果显示了类似的细胞迁移和分化模式，这与体外模型相吻合。有趣的是，生物聚合物基质也允许体内新生血管的形成。
Epithelial-mesenchymal interactions play a key role in the development of tissues such as tooth, lungs, and kidneys. To successfully engineer or repair such living tissues it is necessary to first understand the complex cell cell and cell-matrix interactions underlying organogenesis. To mimic an in vivo setting it is necessary to assemble a three-dimensional matrix that would facilitate cell-cell interaction leading to proliferation and cellular differentiation. In this study, we have developed an in vitro three-dimensional multilayered coculture system using type I collagen and chitosan blends as matrices, to study epithelial-mesenchymal interactions that occur during tooth morphogenesis. Results from this study showed that the matrix composition influenced the migration, proliferation, and differentiation properties of the epithelial and mesenchymal cells. Specifically, the system supported the migration and differentiation of the HAT-7 epithelial cells and mesenchymal-derived dental pulp stem cells. Results from the in vivo implantation study of the coculture system in mice demonstrated a similar cellular migration and differentiation pattern that corroborates well with the in vitro model. Interestingly, the biopolymer matrix also permitted neovascularization in vivo.