title: The metabolism of human mesenchymal stem cells during proliferation and differentiation.
abstract: Human mesenchymal stem cells (MSCs) reside under hypoxic conditions in vivo, between 4% and 7% oxygen. Differentiation of MSCs under hypoxic conditions results in inhibited osteogenesis, while chondrogenesis is unaffected. The reasons for these results may be associated with the inherent metabolism of the cells. The present investigation measured the oxygen consumption, glucose consumption and lactate production of MSCs during proliferation and subsequent differentiation towards the osteogenic and chondrogenic lineages. MSCs expanded under normoxia had an oxygen consumption rate of ∼98 fmol/cell/h, 75% of which was azide-sensitive, suggesting that these cells derive a significant proportion of ATP from oxidative phosphorylation in addition to glycolysis. By contrast, MSCs differentiated towards the chondrogenic lineage using pellet culture had significantly reduced oxygen consumption after 24 h in culture, falling to ∼12 fmol/cell/h after 21 days, indicating a shift towards a predominantly glycolytic metabolism. By comparison, MSCs retained an oxygen consumption rate of ∼98 fmol/cell/h over 21 days of osteogenic culture conditions, indicating that these cells had a more oxidative energy metabolism than the chondrogenic cultures. In conclusion, osteogenic and chondrogenic MSC cultures appear to adopt the balance of oxidative phosphorylation and glycolysis reported for the respective mature cell phenotypes. The addition of TGF-β to chondrogenic pellet cultures significantly enhanced glycosaminoglycan accumulation, but caused no significant effect on cellular oxygen consumption. Thus, the differences between the energy metabolism of chondrogenic and osteogenic cultures may be associated with the culture conditions and not necessarily their respective differentiation.
authors.affiliation: School of Engineering and Materials Science, Queen Mary University of London, London, UK.
authors.forename: Girish
authors.initials: G
authors.lastname: Pattappa
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Heywood
authors.forename: Joost D
authors.initials: JD
authors.lastname: de Bruijn
authors.forename: David A
authors.initials: DA
authors.lastname: Lee
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010011:Osteocytes / Q000166:cytology; D010101:Oxygen Consumption / Q000502:physiology; D053782:Transforming Growth Factor beta3 / Q000502:physiology
chemical_list: D053782:Transforming Growth Factor beta3; D019344:Lactic Acid; D005947:Glucose