Abstract
BackgroundHuman mesenchymal stem cells (hMSCs) are, due to their pluripotency, useful sources of cells for stem cell therapy and tissue regeneration. The phenotypes of hMSCs are strongly influenced by their microenvironment, in particular the extracellular matrix (ECM), the composition and structure of which are important in regulating stem cell fate. In reciprocal manner, the properties of ECM are remodeled by the hMSCs, but the mechanism involved in ECM remodeling by hMSCs under topographical stimulus is unclear. In this study, we therefore examined the effect of nanotopography on the expression of ECM proteins by hMSCs by analyzing the quantity and structure of the ECM on a nanogrooved surface.MethodsTo develop the nanoengineered, hMSC-derived ECM, we fabricated the nanogrooves on a coverglass using a UV-curable polyurethane acrylate (PUA). Then, hMSCs were cultivated on the nanogrooves, and the cells at the full confluency were decellularized. To analyze the effect of nanotopography on the hMSCs, the hMSCs were re-seeded on the nanoengineered, hMSC-derived ECM.ResultshMSCs cultured within the nano-engineered hMSC-derived ECM sheet showed a different pattern of expression of ECM proteins from those cultured on ECM-free, nanogrooved surface. Moreover, hMSCs on the nano-engineered ECM sheet had a shorter vinculin length and were less well-aligned than those on the other surface. In addition, the expression pattern of ECM-related genes by hMSCs on the nanoengineered ECM sheet was altered. Interestingly, the expression of genes for osteogenesis-related ECM proteins was downregulated, while that of genes for chondrogenesis-related ECM proteins was upregulated, on the nanoengineered ECM sheet.ConclusionsThe nanoengineered ECM influenced the phenotypic features of hMSCs, and that hMSCs can remodel their ECM microenvironment in the presence of a nanostructured ECM to guide differentiation into a specific lineage.
Highlights
Human mesenchymal stem cells are, due to their pluripotency, useful sources of cells for stem cell therapy and tissue regeneration
We examined the effect of nanotopography on the expression of extracellular matrix (ECM) proteins by Human mesenchymal stem cells (hMSCs) by analyzing the quantity and structure of the ECM on a nanogrooved surface
ECM protein production To investigate the effect of nanogrooves on hMSC-derived ECM structure and composition, hMSCs were cultured for 2 weeks to full confluency and immunostained for the following ECM proteins: fibronectin; collagen types I, II, and IV; and laminin (Fig. 2a, b)
Summary
Human mesenchymal stem cells (hMSCs) are, due to their pluripotency, useful sources of cells for stem cell therapy and tissue regeneration. The phenotypes of hMSCs are strongly influenced by their microenvironment, in particular the extracellular matrix (ECM), the composition and structure of which are important in regulating stem cell fate. HMSCs are useful sources for stem cell therapy and tissue regeneration; for the latter application, hMSCs are believed to differentiate and replace damaged cells. In addition to their differentiation potential, environment-remodeling activity of MSCs may affect the success of hMSC-based therapies. Chen’s group reported that differentiation of hMSCs into specific lineages resulted in dynamic changes in the composition of ECM proteins and that sequentially promoted further differentiation of hMSCs [28,29,30]
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