Department of Chemical and Biomolecular Engineering and KI for Nano Century, Korea Advanced of Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
Department of Mechanical Engineering, Korea Advanced of Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
ACS Biomater Sci Eng. 2020 Apr 13;6(4):2240-2250. doi: 10.1021/acsbiomaterials.9b01738. Epub 2020 Mar 9.
The aggregation of mesenchymal stem cells (MSCs) into three-dimensional (3D) spheroids has emerged as a promising therapeutic candidate for the treatment of a variety of diseases. In spite of the numerous 3D culture methods suggested recently for MSC spheroid generation, it is still elusive to fully reflect real stem cell niches; this effort majorly suffers from a lack of cell-extracellular matrix (ECM) interactions within the 3D spheroids. In this study, we develop a simple but versatile method for generating human MSC (hMSC) spheroids by culturing the cells on a functional polymer film surface, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4). Interestingly, the pV4D4-coated surface allows a dynamic cell adhesion to the polymer surface while developing the formation of 3D spheroids. The corresponding mechanotransduction promotes the expression of the endogenous ECM and, in turn, results in a remarkable improvement in self-renewal abilities, pro-angiogenic potency, and multilineage differentiation capabilities. This observation highlights the significance of our method compared to the conventional spheroid-generating methods in terms of recreating the ECM-rich microenvironment. We believe the developed surface can serve as a versatile but reliable method for stem cell-based tissue engineering and regenerative medicine.
间质干细胞（MSCs）的三维（3D）球状体聚集已成为治疗多种疾病的有前途的治疗候选物。尽管最近提出了许多用于 MSC 球体生成的 3D 培养方法，但仍然难以完全反映真实的干细胞生态位；这主要是由于 3D 球体中细胞-细胞外基质（ECM）相互作用的缺乏。在这项研究中，我们通过在功能聚合物膜表面聚（2,4,6,8-四乙烯基-2,4,6,8-四甲基环四硅氧烷）（pV4D4）上培养细胞，开发了一种简单但通用的生成人 MSC（hMSC）球体的方法。有趣的是，pV4D4 涂层表面允许细胞在形成 3D 球体的同时动态地附着在聚合物表面上。相应的力学转导促进了内源性 ECM 的表达，从而显著提高了自我更新能力、促血管生成能力和多能分化能力。与传统的球体生成方法相比，这种观察强调了我们的方法在再现富含 ECM 的微环境方面的重要性。我们相信，所开发的表面可以作为基于干细胞的组织工程和再生医学的一种通用但可靠的方法。
