Gupta Dhanak, Grant David M, Zakir Hossain Kazi M, Ahmed Ifty, Sottile Virginie
1 Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, University of Nottingham, Nottingham, UK.
2 Advanced Materials Research Group, Faculty of Engineering, University of Nottingham, UK.
J Biomater Appl. 2018 Feb;32(7):906-919. doi: 10.1177/0885328217745699. Epub 2017 Dec 13.
Mesenchymal stem cells play a vital role in bone formation process by differentiating into osteoblasts, in a tissue that offers not a flat but a discontinuous three-dimensional (3D) topography in vivo. In order to understand how geometry may be affecting mesenchymal stem cells, this study explored the influence of 3D geometry on mesenchymal stem cell-fate by comparing cell growth, viability and osteogenic potential using monolayer (two-dimensional, 2D) with microsphere (3D) culture systems normalised to surface area. The results suggested lower cell viability and reduced cell growth in 3D. Alkaline phosphatase activity was higher in 3D; however, both collagen and mineral deposition appeared significantly lower in 3D, even after osteogenic supplementation. Also, there were signs of patchy mineralisation in 3D with or without osteogenic supplementation as early as day 7. These results suggest that the convex surfaces on microspheres and inter-particulate porosity may have led to variable cell morphology and fate within the 3D culture. This study provides deeper insights into geometrical regulation of mesenchymal stem cell responses applicable for bone tissue engineering.
间充质干细胞在骨形成过程中发挥着至关重要的作用，它可分化为成骨细胞，而在体内，其所处组织提供的并非平坦的而是不连续的三维（3D）地形结构。为了了解几何形状如何影响间充质干细胞，本研究通过比较使用归一化至表面积的单层（二维，2D）与微球（3D）培养系统中的细胞生长、活力和成骨潜能，探讨了3D几何形状对间充质干细胞命运的影响。结果表明，3D环境下细胞活力较低且细胞生长减少。3D环境中碱性磷酸酶活性较高；然而，即使在进行成骨补充后，3D环境中胶原蛋白和矿物质沉积均显著较低。此外，早在第7天，无论有无成骨补充，3D环境中都有斑片状矿化的迹象。这些结果表明，微球上的凸面和颗粒间孔隙可能导致了3D培养内细胞形态和命运的变化。本研究为适用于骨组织工程的间充质干细胞反应的几何调控提供了更深入的见解。
