Cosson S, Lutolf M P
School of Life Sciences, Institute of Bioengineering and Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Sci Rep. 2014 Mar 25;4:4462. doi: 10.1038/srep04462.
Biomolecular signaling is of utmost importance in governing many biological processes such as the patterning of the developing embryo where biomolecules regulate key cell-fate decisions. In vivo, these factors are presented in a spatiotemporally tightly controlled fashion. Although state-of-the-art microfluidic technologies allow precise biomolecule delivery in time and space, long-term (stem) cell culture at the micro-scale is often far from ideal due to medium evaporation, limited space for cell growth or shear stress. To overcome these challenges, we here introduce a concept based on hydrogel microfluidics for decoupling conventional, macro-scale cell culture from precise biomolecule delivery through a gel layer. We demonstrate the spatiotemporally controlled neuronal commitment of mouse embryonic stem cells via delivery of retinoic acid gradients. This technique should be useful for testing the effect of dose and timing of biomolecules, singly or in combination, on stem cell fate.
生物分子信号传导在调控许多生物过程中至关重要，例如在发育胚胎的模式形成过程中，生物分子调节关键的细胞命运决定。在体内，这些因子以时空紧密控制的方式呈现。尽管先进的微流控技术能够在时间和空间上精确递送生物分子，但由于培养基蒸发、细胞生长空间有限或剪切应力等原因，微尺度下的长期（干）细胞培养往往远非理想状态。为了克服这些挑战，我们在此引入一种基于水凝胶微流控的概念，通过凝胶层将传统的宏观尺度细胞培养与精确的生物分子递送解耦。我们通过视黄酸梯度的递送，证明了对小鼠胚胎干细胞进行时空控制的神经元定向分化。该技术对于测试生物分子单独或组合使用时的剂量和时间对干细胞命运的影响应该是有用的。
