Chen Yazhou, Lee Kyubae, Chen Ying, Yang Yingnan, Kawazoe Naoki, Chen Guoping
Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 3050044, Japan.
Department of Materials Science and Engineering, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
ACS Biomater Sci Eng. 2019 Nov 11;5(11):6099-6108. doi: 10.1021/acsbiomaterials.9b00866. Epub 2019 Oct 9.
Extracellular matrixes (ECMs) play a vital role in controlling cell functions because of their similarity to the in vivo microenvironment. The composition of ECMs is not constant but dynamically remolded during stem cell differentiation and tissue development. Development of three-dimensional (3D) biomimetic ECM scaffolds is desirable for investigation of ECM-cell interactions and tissue engineering applications. Here, 3D ECM scaffolds that mimicked the dynamic ECM remodeling during stepwise adipogenesis of human mesenchymal stem cells (hMSCs) were developed. A biodegradable hybrid mesh of poly-(dl-lactic-co-glycolic acid) and collagen was used as a template for cell culture. hMSCs were cultured in the hybrid mesh, and their adipogenic differentiation was controlled at early, late, and undifferentiated stages. Three types of stepwise 3D ECM hybrid scaffolds were prepared from the cultured cells after decellularization. They are mesenchymal stem cell ECM scaffold (SC-ECM scaffold), early-stage adipogenesis-mimicking ECM scaffold (EA-ECM scaffold), and late-stage adipogenesis-mimicking ECM scaffold (LA-ECM scaffold). The stepwise 3D ECM scaffolds had a different composition that was dependent on the differentiation stage of hMSCs. They also showed a different influence on the adipogenic differentiation of hMSCs. The EA-ECM scaffold promoted, while the SC-ECM and LA-ECM scaffolds inhibited the adipogenic differentiation of hMSCs.
细胞外基质（ECM）因其与体内微环境相似，在控制细胞功能方面发挥着至关重要的作用。ECM的组成并非恒定不变，而是在干细胞分化和组织发育过程中动态重塑。开发三维（3D）仿生ECM支架对于研究ECM与细胞的相互作用以及组织工程应用具有重要意义。在此，我们开发了一种3D ECM支架，它模拟了人骨髓间充质干细胞（hMSC）逐步脂肪生成过程中的动态ECM重塑。一种由聚（dl - 乳酸 - 乙醇酸共聚物）和胶原蛋白组成的可生物降解混合网被用作细胞培养的模板。hMSC在混合网中培养，其脂肪生成分化在早期、晚期和未分化阶段受到控制。在脱细胞后，从培养的细胞中制备了三种类型的逐步3D ECM混合支架。它们分别是间充质干细胞ECM支架（SC - ECM支架）、模拟早期脂肪生成的ECM支架（EA - ECM支架）和模拟晚期脂肪生成的ECM支架（LA - ECM支架）。逐步3D ECM支架具有不同的组成，这取决于hMSC的分化阶段。它们对hMSC的脂肪生成分化也表现出不同的影响。EA - ECM支架促进hMSC的脂肪生成分化，而SC - ECM和LA - ECM支架则抑制hMSC的脂肪生成分化。
