title: Lactate influences the gene expression profile of human mesenchymal stem cells (hMSC) in a dose dependant manner.
abstract: OBJECTIVE
  Wounds, especially non-healing wounds are characterized by elevated tissue lactate concentrations. Lactate is known for being able to stimulate collagen synthesis and vessel growth. Lately it has been shown that lactate, in vivo, plays an important role in homing of stem cells. With this work we aimed to show the influence of lactate on the gene expressionprofile of human mesenchymal stem cells (hMSC).
  
  
  METHODS
  hMSCs were obtained from bone marrow and characterized with fluorescence-activated cell sorting (FACS) analysis. Subsequently the hMSCs were treated with either 0, 5, 10 and 15 mM lactate (pH 7,4) for 24 hours. RNA Isolation from stimulated hMSCs and controls was performed. The Microarray analysis was performed using AffymetrixHuGene 1.0 ST Gene Chip. Selected targets were subsequently analysed using quantitative real time PCR (RTq-PCR).
  
  
  RESULTS
  We were able to show that lactate in moderate concentrations of 5 respectively 10 mM leads to an anti-inflammatory, anti-apoptotic but growth and proliferation promoting gene expression after 24 h. In contrast, high lactate concentrations of 15 mM leads to the opposed effect, namely promoting inflammation and apoptosis. Hypoxia induced genes did not show any significant regulation. Contrary to expectation, we were not able to show any significant regulation of candidates associated with glycolysis.
  
  
  CONCLUSIONS
  We were able to show that lactate alters gene expression but does not change the cell phenotype, which might be helpful for further investigations of new treatment strategies for chronic non-healing wounds as well as tumor-therapy and neuronal plasticity.
authors.affiliation: Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, Tuebingen, Germany.
authors.forename: Carl-Christoph
authors.initials: CC
authors.lastname: Schneider
authors.forename: Atesch
authors.initials: A
authors.lastname: Ateschrang
authors.forename: Ingmar
authors.initials: I
authors.lastname: Königsrainer
authors.forename: Jörg
authors.initials: J
authors.lastname: Glatzle
authors.forename: Sarah
authors.initials: S
authors.lastname: Bühler
authors.forename: Richard
authors.initials: R
authors.lastname: Schaefer
authors.forename: Hinnak
authors.initials: H
authors.lastname: Northoff
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Derek
authors.initials: D
authors.lastname: Zieker
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D059470:Tetraspanins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing
chemical_list: D051017:Apoptosis Regulatory Proteins; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; C502874:TSPAN13 protein, human; C512650:TSPAN2 protein, human; D059470:Tetraspanins; D053773:Transforming Growth Factor beta1; D019344:Lactic Acid