Al Hosni Rawiya, Bozec Laurent, Roberts Scott J, Cheema Umber
UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Sciences, University College London, 43-45 Foley St, Fitzrovia, W1W 7TY London, UK.
Faculty of Dentistry, University of Toronto, 12 Edward Street, Toronto, ON M5G 1G6, Canada.
iScience. 2022 Mar 11;25(4):104059. doi: 10.1016/j.isci.2022.104059. eCollection 2022 Apr 15.
The biophysical microenvironment of the cell is being increasingly used to control cell signaling and to direct cell function. Herein, engineered 3D tuneable biomimetic scaffolds are used to control the cell microenvironment of Adipose-derived Mesenchymal Stromal Cells (AMSC), which exhibit a collagen density-specific profile for early and late stage bone cell lineage status. Cell potency was enhanced when AMSCs were cultured within low collagen density environments in hypoxic conditions. A transitional culture containing varied collagen densities in hypoxic conditions directed differential cell fate responses. The early skeletal progenitor identity (PDPNCD146CD73CD164) was rescued in the cells which migrated into low collagen density gels, with cells continuously exposed to the high collagen density gels displaying a transitioned bone-cartilage-stromal phenotype (PDPNCD146CD73CD164). This study uncovers the significant contributions of the physical and physiological cell environment and highlights a chemically independent methodology for reprogramming and isolating skeletal progenitor cells from an adipose-derived cell population.
细胞的生物物理微环境正越来越多地用于控制细胞信号传导并指导细胞功能。在此，工程化的3D可调仿生支架被用于控制脂肪来源的间充质基质细胞（AMSC）的细胞微环境，这些细胞表现出针对早期和晚期骨细胞谱系状态的胶原密度特异性特征。当AMSC在低氧条件下的低胶原密度环境中培养时，细胞潜能得到增强。在低氧条件下含有不同胶原密度的过渡培养引导了不同的细胞命运反应。迁移到低胶原密度凝胶中的细胞恢复了早期骨骼祖细胞身份（PDPNCD146CD73CD164），而持续暴露于高胶原密度凝胶中的细胞则表现出转变后的骨-软骨-基质表型（PDPNCD146CD73CD164）。这项研究揭示了物理和生理细胞环境的重要贡献，并突出了一种从脂肪来源的细胞群体中对骨骼祖细胞进行重编程和分离的化学独立方法。
