title: Short-term mechanical stretch fails to differentiate human adipose-derived stem cells into cardiovascular cell phenotypes.
abstract: BACKGROUND
  We and others have previously demonstrated that adipose-derived stem cells (ASCs) transplantation improve cardiac dysfunction post-myocardium infarction (MI) under hemodynamic stress in rats. The beneficial effects appear to be associated with pleiotropic factors due to a complex interplay between the transplanted ASCs and the microenvironment in the absence of cell transdifferentiation. In the present work, we tested the hypothesis that mechanical stretch per se could change human ASCs (hASCs) into cardiovascular cell phenotypes that might influence post-MI outcomes.
  
  
  METHODS
  Human ASCs were obtained from patients undergoing liposuction procedures. These cells were stretched 12%, 1Hz up to 96 hours by using Flexercell 4000 system. Protein and gene expression were evaluated to identify cardiovascular cell markers. Culture medium was analyzed to determine cell releasing factors, and contraction potential was also evaluated.
  
  
  RESULTS
  Mechanical stretch, which is associated with extracellular signal-regulated kinase (ERK) phosphorylation, failed to induce the expression of cardiovascular cell markers in human ASCs, and mesenchymal cell surface markers (CD29; CD90) remained unchanged. hASCs and smooth muscle cells (SMCs) displayed comparable contraction ability. In addition, these cells demonstrated a profound ability to secrete an array of cytokines. These two properties of human ASCs were not influenced by mechanical stretch.
  
  
  CONCLUSIONS
  Altogether, our findings demonstrate that hASCs secrete an array of cytokines and display contraction ability even in the absence of induction of cardiovascular cell markers or the loss of mesenchymal surface markers when exposed to mechanical stretch. These properties may contribute to beneficial post-MI cardiovascular outcomes and deserve to be further explored under the controlled influence of other microenvironment components associated with myocardial infarction, such as tissue hypoxia.
authors.forename: Thais
authors.initials: T
authors.lastname: Girão-Silva
authors.forename: Vinicius
authors.initials: V
authors.lastname: Bassaneze
authors.forename: Luciene Cristina Gastalho
authors.initials: LC
authors.lastname: Campos
authors.forename: Valerio Garrone
authors.initials: VG
authors.lastname: Barauna
authors.forename: Luis Alberto Oliveira
authors.initials: LA
authors.lastname: Dallan
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor) - University of São Paulo School of Medicine, Avenue Dr, Eneas de Carvalho Aguiar, 44, São Paulo, SP 05403-000, Brazil. krieger@incor.usp.br.
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Ayumi Aurea
authors.initials: AA
authors.lastname: Miyakawa
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D002319:Cardiovascular System / Q000166:cytology*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D055595:Mechanical Phenomena; D009203:Myocardial Infarction / Q000601:surgery; D010641:Phenotype; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10