De Bank Paul A, Hou Qingpu, Warner Robert M, Wood Ian V, Ali Bahaa E, Macneil Sheila, Kendall David A, Kellam Barrie, Shakesheff Kevin M, Buttery Lee D K
Department of Pharmacy & Pharmacology, University of Bath, Bath BA2 7AY, UK.
Biotechnol Bioeng. 2007 Aug 15;97(6):1617-25. doi: 10.1002/bit.21343.
The three-dimensional (3-D) arrangement of cells within tissues is integral to their development and function. Advances in stem cell science and regenerative medicine have stimulated interest in the replication of this architecture in vitro. We have developed a versatile method for controlling short-term cell-cell and cell-matrix interactions via a facile cell surface engineering process that enables the rapid formation of specific 3-D interactions for a range of cell types. We demonstrate that chemical modification of cell surfaces and matrix proteins can artificially accelerate the cell adhesion process and confirm the ability to control the formation of multicellular aggregates with defined architectures and heterotypic cell types. Direct comparison with a natural aggregation process seen during differentiation of embryonic stem (ES) cells revealed increased expression of developmental regulatory proteins and a concomitant enhancement of ES cell differentiation. Furthermore, this new methodology has numerous applications in generating layered structures. For example, we demonstrate improved transfer of therapeutic human keratinocytes onto a dermal layer in a skin repair model.
组织内细胞的三维（3-D）排列对于其发育和功能至关重要。干细胞科学和再生医学的进展激发了人们在体外复制这种结构的兴趣。我们开发了一种通用方法，通过简便的细胞表面工程过程来控制短期细胞 - 细胞和细胞 - 基质相互作用，该过程能够为一系列细胞类型快速形成特定的3-D相互作用。我们证明，细胞表面和基质蛋白的化学修饰可以人为加速细胞粘附过程，并证实能够控制具有明确结构和异型细胞类型的多细胞聚集体的形成。与胚胎干细胞（ES）分化过程中自然聚集过程的直接比较显示，发育调节蛋白的表达增加，同时ES细胞分化增强。此外，这种新方法在生成层状结构方面有许多应用。例如，我们在皮肤修复模型中证明了治疗性人角质形成细胞向真皮层的转移得到了改善。
