Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories 999077, Hong Kong, China.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Collage of Biophotonics, South China Normal University, Guangzhou, 510631, China.
Biomaterials. 2018 Aug;173:87-99. doi: 10.1016/j.biomaterials.2018.05.001. Epub 2018 May 4.
Stem cells reside in a three-dimensional (3D) niche microenvironment, which provides specific cues, including cell-matrix interactions and soluble factors, that are essential to the differentiation of stem cells in vivo. Herein we demonstrate a general approach to the synthetic reconstruction of 3D biomimetic niche environment of stem cells by the multiscale combination of macroscopic porous hydrogels and a nanoscale upconversion nanoparticles (UCNP)-based nanocomplex. The porous biopolymeric hydrogels emulate the spongy bone microstructure and provide 3D environment conducive to the differentiation of seeded stem cells. The UCNP-based nanocomplex (Pur-UCNP-peptide-FITC), which is stably encapsulated in the porous hydrogels, emulates the repertoire of inductive factors in bone matrix by maintaining localized long-term delivery of inductive small molecules. The nanocomplex also generates biomarker-specific reporting emissions that correlate with the extent and stage of differentiation of the stem cells in synthetic niche, thereby allowing long-term tracking of stem cell fate in a non-contact, non-destructive, and potentially high-throughput manner in living cultures. To the best of our knowledge, this is first demonstration of synthetic niche reconstruction. The modular nature of this synthetic niche platform allows various parameters to be easily tuned to accommodate a variety of fundamental studies of dynamic cellular events under controlled settings.
干细胞存在于三维（3D）的微环境中，这个微环境提供了特定的信号，包括细胞-基质相互作用和可溶性因子，这些信号对于干细胞在体内的分化是必不可少的。在这里，我们通过宏观多孔水凝胶和基于上转换纳米粒子（UCNP）的纳米复合物的多尺度组合，展示了一种通用的方法来合成重建干细胞的 3D 仿生微环境。多孔生物聚合物水凝胶模拟海绵骨的微观结构，并提供有利于种子干细胞分化的 3D 环境。基于 UCNP 的纳米复合物（Pur-UCNP-肽-FITC）稳定地封装在多孔水凝胶中，通过局部长期输送诱导小分子来模拟骨基质中的诱导因子库。纳米复合物还产生与干细胞在合成微环境中分化程度和阶段相关的生物标志物特异性报告发射，从而允许以非接触、非破坏性且潜在高通量的方式在活培养物中对干细胞命运进行长期跟踪。据我们所知，这是首次对合成微环境进行重建的演示。这种合成微环境平台的模块化性质允许轻松调整各种参数，以适应各种在受控环境下进行的动态细胞事件的基础研究。
