Influence of surface topographic microstructure on behaviors of multipotent and pluripotent stem cells

Abstract

Objective: Using mechanical cues to control stem cells fate has attracted the widespread attention in the field of stem cell-based regenerative therapies. The aim of the present work was to determine the influence of surface microstructures (curvature level) on secretome, migration of human mesenchymal stem cells (MSCs) and to reveal the underlying mechanism. Furthermore, the efficiency of the neural differentiation of human induce pluripotent stem cells (iPSCs) on the surface with microstructures was evaluated. Methods: Human adipose derived mesenchymal stem cells (ADSCs) were cultivated on polystyrene surfaces with different curvature levels. Conditioned medium from such cultures was collected and its VEGF levels were analyzed. Further, the cells preconditioned by the surface curvatures were collected and reseeded on regular tissue culture plates to examine their migration capacity. For the underlying mechanism, the activation level of integrin, focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK/ERK) were measured. Using matrigel coated polystyrene surface with different curvature levels for cultivation, human induced pluripotent stem cells (iPSCs) were induced to differentiate into neural lineages. Expression level of neural genes and protein was analyzed to evaluate the differentiation efficiency. Results: Appropriate surface topographic curvature promoted the VEGF secretion of human ADSCs. The conditioned medium increased tube formation and migration of human umbilical vein endothelial cells (HUVECs) in vitro and stimulated blood vessels formation in the hen's egg test - chorioallantoic membrane (HET-CAM) ex vivo. For the underlying mechanism, the integrin mediated FAK-MAPK/ERK pathway was involved in the surface curvatures stimulated ADSCs behavior. Furthermore, the curvature was found to increase the neural differentiation efficiency of human iPSCs. Conclusion: Surface with microscale curvature increases VEGF secretion and migration capacity of MSCs via activating the integrin mediated FAK-MAPK/ERK signaling pathway, but this regulation effect is depended on the curvature level. Further, the similar surface can promote the neural differentiation of human iPSCs. Surface microscale curvature might be a useful strategy to enhance the therapeutic potential of stem cells in regenerative medicine.