Division of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore.
Adv Drug Deliv Rev. 2011 Apr 30;63(4-5):277-90. doi: 10.1016/j.addr.2011.03.003. Epub 2011 Mar 8.
With the advent of multicellular organisms, the exterior of the cells evolved dramatically from highly aqueous surroundings into an extracellular matrix and space crowded with macromolecules. Cell-based therapies require removal of cells from their crowded physiological context and propagating them in dilute culture medium to attain therapeutically relevant numbers whilst preserving their phenotype. However, bereft of their microenvironment, cells under perform and lose functionality. Major efforts currently aim to modify cell culture surfaces and build three dimensional scaffolds to improve this situation. We discuss here alternative strategies that enable cells to re-create their own microenvironment in vitro, using carbohydrate-based macromolecules as culture media additives that create an excluded volume effect at defined fraction volume occupancies. This biophysical approach dramatically enhances extracellular matrix deposition by differentiated cells and stem cells, and boosts progenitor cell differentiation and proliferation. We begin to understand how well cells really can perform ex vivo if given the chance.
随着多细胞生物的出现，细胞的外部环境从高度水合的环境剧烈地演变为细胞外基质和充满大分子的空间。基于细胞的治疗需要将细胞从拥挤的生理环境中取出，并在稀有的培养基中繁殖，以达到治疗相关的数量，同时保持其表型。然而，由于缺乏微环境，细胞的表现和功能都会下降。目前的主要努力旨在修饰细胞培养表面并构建三维支架来改善这种情况。我们在这里讨论了替代策略，这些策略可以使细胞在体外重新创造自己的微环境，使用碳水化合物为基础的大分子作为培养基添加剂，在定义的分数体积占有率下产生排除体积效应。这种生物物理方法显著增强了分化细胞和干细胞的细胞外基质沉积，并促进了祖细胞的分化和增殖。如果有机会，我们开始了解细胞在体外能够发挥出多好的性能。
