Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK.
Protein Analysis and Proteomics Platform, The Francis Crick Institute, London, NW1 1AT, UK.
Nat Commun. 2018 Oct 3;9(1):4049. doi: 10.1038/s41467-018-06183-4.
Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells' 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells' reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC's interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.
可调节水凝胶在很大程度上揭示了细胞 3D 环境的物理特性如何驱动干细胞谱系特化。然而，在天然组织中，细胞并非被动地从其龛位接收信号。相反，它们主动探测和修饰其细胞周空间以适应其需要，但当细胞被包裹在水凝胶中时，它们与细胞周环境的相互作用的动力学仍然相对未知。在这里，我们表明，包封在透明质酸基水凝胶中的人骨髓基质细胞（hMSC）通过在细胞周合成、分泌和排列蛋白质或降解水凝胶来修饰其周围环境。hMSC 与局部环境的相互作用在调节 hMSC 命运中起作用，细胞周分泌的蛋白多糖与脂肪生成有关，而降解则与成骨作用有关。我们的观察表明，hMSC 参与其 3D 环境特性与其自身分泌的细胞周基质之间的双向相互作用，并且这种相互作用组合驱动命运。
