The effect of mechanical stress on the proliferation, adipogenic differentiation and gene expression of human adipose-derived stem cells

Abstract

To allow for a better implementation of external volume expansion to clinical applications for soft tissue regeneration, it is necessary to comprehensively understand the underlying mechanisms. As human adipose-derived stem cells (hASCs) play a crucial role in soft tissue enlargement, we investigated the impact of cyclic stretch on gene expression, proliferation rate and adipogenic differentiation of these cells. After cyclic stretching, RNA was extracted and subjected to DNA microarray analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Also, the expression of FABP4 mRNA was analysed by RT-qPCR to test whether mechanical stretch affected adipogenic differentiation of hASCs. The proliferation rate was assessed using the alamarBlue assay and Ki-67 staining. A cell cycle analysis was performed with flow cytometry and Western blot. We found that cyclic stretch significantly induced the expression of CYP1B1 mRNA. Furthermore, the adipogenic differentiation of hASCs was impaired, as was the proliferation. This was partly due to a decrease in extracellular signal-regulated kinase (ERK) 1/2 and histone H3 phosphorylation, suggesting a growth arrest in the G 2 /M phase of the cell cycle. Enrichment analyses demonstrated that stretch-regulated genes were over-represented in pathways and biological processes involved in extracellular matrix organization, vascular remodelling and responses to cell stress. Taken together, mechanical stress impaired both proliferation and adipogenic differentiation, but led to a tissue-remodelling phenotype of hASCs. These data suggest that extracellular matrix remodelling and neoangiogenesis may play a more important role in external volume expansion than proliferation and adipogenesis of hASCs.

An Integrated Bioprocess for the Expansion and Chondrogenic Priming of Human Periosteum‐Derived Progenitor Cells in Suspension Bioreactors

“…mRNA expression of PPAR γ decreased over time suggesting a commitment of the primed cells to an osteochondral lineage. Shear stress has been shown to down‐regulate adipogenic differentiation of adipose derived stem cells and corroborates the decrease in vitro adipogenesis after expansion in our setup. The negative effect of TGF β on adipogenic differentiation of various cell types have also been shown by different groups .…”

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Tackling the Concept of Symbiotic Implantable Medical Devices with Nanobiotechnologies

“…A mechanical stress directly activates the cell membrane: multiple membrane proteins sense and amplify the signal (ion channels, GPCRs, integrins, connexins). But the mechanical signal also has a major impact to modify gene expression indirectly via an internal cascade of events ending by transcription factors . Nonetheless, it remains a one way signaling device leading to encapsulation of the external part and good hemocompatibility brought by biological treated tissues.…”