The effect of equiaxial stretching on the osteogenic differentiation and mechanical properties of human adipose stem cells

• Published in: Journal of the mechanical behavior of biomedical materials Vol. 72; pp. 38 - 48
• Main Authors: Virjula, Sanni, Zhao, Feihu, Leivo, Joni, Vanhatupa, Sari, Kreutzer, Joose, Vaughan, Ted J., Honkala, Anna-Maija, Viehrig, Marlitt, Mullen, Conleth A., Kallio, Pasi, McNamara, Laoise M., Miettinen, Susanna
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.08.2017
• Subjects: Adipose Tissue - cytology; Atomic force microscopy indentation; Cell Differentiation; Cells, Cultured; Dynamic cell culture; Focal Adhesions - physiology; Humans; Mechanical stimulation; mechanobiology; Mesenchymal stem cell; Osteogenesis; PDMS; Stem Cells - cytology; Mesenchymal stem cell; mechanobiology; Mechanical stimulation; Dynamic cell culture; Atomic force microscopy indentation; PDMS
• ISSN: 1751-6161; 1878-0180
• DOI: 10.1016/j.jmbbm.2017.04.016

Although mechanical cues are known to affect stem cell fate and mechanobiology, the significance of such stimuli on the osteogenic differentiation of human adipose stem cells (hASCs) remains unclear. In this study, we investigated the effect of long-term mechanical stimulation on the attachment, osteogenic differentiation and mechanical properties of hASCs. Tailor-made, pneumatic cell stretching devices were used to expose hASCs to cyclic equiaxial stretching in osteogenic medium. Cell attachment and focal adhesions were visualised using immunocytochemical vinculin staining on days 3 and 6, and the proliferation and alkaline phosphatase activity, as a sign of early osteogenic differentiation, were analysed on days 0, 6 and 10. Furthermore, the mechanical properties of hASCs, in terms of apparent Young’s modulus and normalised contractility, were obtained using a combination of atomic force microscopy based indentation and computational approaches. Our results indicated that cyclic equiaxial stretching delayed proliferation and promoted osteogenic differentiation of hASCs. Stretching also reduced cell size and intensified focal adhesions and actin cytoskeleton. Moreover, cell stiffening was observed during osteogenic differentiation and especially under mechanical stimulation. These results suggest that cyclic equiaxial stretching modifies cell morphology, focal adhesion formation and mechanical properties of hASCs. This could be exploited to enhance osteogenic differentiation. [Display omitted] •Equiaxial stretching enhances osteogenic differentiation of adipose stem cells.•Stretching reduces cell size and intensifies focal adhesions and actin cytoskeleton.•Cellular Young’s modulus increases during osteogenic differentiation.