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.

中文翻译：

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聚合物涂层表面上的三维球体培养通过增强的细胞-细胞外基质相互作用增强干细胞功能

间充质干细胞（MSCs）聚集到三维（3D）球体中已成为一种有希望的治疗各种疾病的治疗候选物。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出真实的干细胞壁still。这种努力主要是因为3D椭球体缺少细胞-细胞外基质（ECM）相互作用。在这项研究中，我们开发了一种通过在功能性聚合物膜表面poly（2,4,6,8-tetravinyl-2,4,6,8--）上培养细胞来生成人MSC（hMSC）球体的简单但通用的方法。四甲基环四硅氧烷）（pV4D4）。有趣的是，涂有pV4D4的表面在形成3D椭球体的同时，允许动态细胞粘附到聚合物表面。相应的机械转导促进了内源性ECM的表达，进而导致自我更新能力，促血管生成能力和多系分化能力的显着提高。该观察结果凸显了我们的方法与传统的球体生成方法相比在重建ECM丰富的微环境方面的重要性。我们相信，已开发的表面可作为基于干细胞的组织工程和再生医学的通用但可靠的方法。该观察结果凸显了我们的方法与传统的球体生成方法相比在重建ECM丰富的微环境方面的重要性。我们相信，已开发的表面可作为基于干细胞的组织工程和再生医学的通用但可靠的方法。该观察结果凸显了我们的方法与传统的球体生成方法相比在重建ECM丰富的微环境方面的重要性。我们相信，已开发的表面可作为基于干细胞的组织工程和再生医学的通用但可靠的方法。