title: 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 G2/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. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Plastic Surgery and Hand Surgery - Burn Center, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Paul
authors.affiliation: Interdisciplinary Center for Clinical Research, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Denecke
authors.affiliation: Department of Plastic Surgery and Hand Surgery - Burn Center, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Bong-Sung
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Institute of Neuropathology, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Dreser
authors.affiliation: Department of Vascular Biology, Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians-University (LMU) of Munich, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bernhagen
authors.affiliation: Department of Plastic Surgery and Hand Surgery - Burn Center, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pallua
mesh_terms: D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology*; D002453:Cell Cycle; D049109:Cell Proliferation; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D063990:Gene Ontology; D006801:Humans; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1
keywords: CYP1B1; ERK1/2; adipogenic differentiation; cell cycle; external volume expansion; human adipose-derived stem cells; mechanical stress