School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116023, P. R. China.
School of Engineering and Applied Science, Harvard University, 9 Oxford St, Cambridge, MA, 02138, USA.
Small. 2018 Mar;14(9). doi: 10.1002/smll.201702955. Epub 2018 Jan 15.
Controlled encapsulation and pairing of single cells within a confined 3D matrix can enable the replication of the highly ordered cellular structure of human tissues. Microgels with independently controlled compartments that can encapsulate cells within separately confined hydrogel matrices would provide precise control over the route of pairing single cells. Here, a one-step microfluidic method is presented to generate monodisperse multicompartment microgels that can be used as a 3D matrix to pair single cells in a highly biocompatible manner. A method is presented to induce microgels formation on chip, followed by direct extraction of the microgels from oil phase, thereby avoiding prolonged exposure of the microgels to the oil. It is further demonstrated that by entrapping stem cells with niche cells within separate but adjacent compartments of the microgels, it can create complex stem cell niche microenvironments in a controlled manner, which can serve as a useful tool for the study of cell-cell interactions. This microfluidic technique represents a significant step toward high-throughput single cells encapsulation and pairing for the study of intercellular communications at single cell level, which is of significant importance for cell biology, stem cell therapy, and tissue engineering.
在受限的 3D 基质中对单个细胞进行受控包封和配对,可以复制人体组织中高度有序的细胞结构。具有独立控制隔室的微凝胶可以将细胞封装在单独受限的水凝胶基质内,从而可以精确控制单个细胞配对的途径。这里提出了一种一步微流控方法来生成单分散多隔室微凝胶,可将其用作 3D 基质,以高度生物相容的方式配对单个细胞。提出了一种在芯片上诱导微凝胶形成的方法,然后直接从油相提取微凝胶,从而避免了微凝胶长时间暴露在油中。进一步证明,通过将干细胞与微凝胶的相邻隔室中的龛细胞一起包封,可以以受控的方式创建复杂的干细胞龛微环境,这可以作为研究细胞间相互作用的有用工具。这种微流控技术代表了在单细胞水平上研究细胞间通讯的高通量单个细胞包封和配对的重要一步,对于细胞生物学、干细胞治疗和组织工程具有重要意义。