title: Low ATP level is sufficient to maintain the uncommitted state of multipotent mesenchymal stem cells.
abstract: BACKGROUND
  Multipotent mesenchymal stromal cells (MMSCs) are minimally differentiated precursors with great potential to transdifferentiate. These cells are quite resistant to oxygen limitation, suggesting that a hypoxic milieu can be physiological for MMSCs.
  
  
  METHODS
  Human MMSCs isolated from adipose tissue were grown at various oxygen concentrations. Alteration in cell immunophenotype was determined by flow cytometry after staining with specific antibodies. Concentrations of glucose and lactate were determined using the Biocon colorimetric test. Cellular respiration was assessed using oxygen electrode. The modes of cell death were analyzed by flow cytometry after staining with Annexin V and propidium iodide.
  
  
  RESULTS
  We found that permanent oxygen deprivation attenuated cellular ATP levels in these cells, diminishing mitochondrial ATP production but stimulating glycolytic ATP production. At the same time, permanent hypoxia did not affect MMSCs' viability, stimulated their proliferation and reduced their capacity to differentiate. Further, permanent hypoxia decreased spontaneous cell death by MMSCs.
  
  
  CONCLUSIONS
  Under hypoxic conditions glycolysis provides sufficient energy to maintain MMSCs in an uncommitted state.
  
  
  CONCLUSIONS
  These findings are of interest not only for scientific reasons, but also in practical terms. Oxygen concentration makes an essential contribution to MMSC physiology and should be taken into account in the setting of protocols for cellular therapy.
authors.affiliation: Faculty of Basic Medicine, MV Lomonosov Moscow State University, Moscow, Russia.
authors.forename: L B
authors.initials: LB
authors.lastname: Buravkova
authors.forename: Y V
authors.initials: YV
authors.lastname: Rylova
authors.forename: E R
authors.initials: ER
authors.lastname: Andreeva
authors.forename: A V
authors.initials: AV
authors.lastname: Kulikov
authors.forename: M V
authors.initials: MV
authors.lastname: Pogodina
authors.forename: B
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: V
authors.initials: V
authors.lastname: Gogvadze
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D010100:Oxygen
keywords: ATP; Cell death; Hypoxia; Multipotent mesenchymal stromal cells