Hyperbaric oxygen induces placental growth factor expression in bone marrow-derived mesenchymal stem cells

Life Sci. 2008 Jul 4;83(1-2):65-73. doi: 10.1016/j.lfs.2008.05.005. Epub 2008 May 23.


The bone marrow is home to mesenchymal stem cells (MSCs) that are able to differentiate into many different cell types. The effect of hyperbaric oxygen (HBO) on MSCs is poorly understood. Placental growth factor (PlGF) is an attractive therapeutic agent for stimulating revascularization of ischemic tissue. HBO has been shown to improve diabetic wound healing by increase circulating stem cells. We hypothesized that HBO induces PlGF expression in bone marrow-derived MSCs. The MSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of MSCs were identified by flow cytometry and immunophenotyping. HBO at 2.5 ATA (atmosphere absolute) significantly increased PlGF protein and mRNA expression. The induction of PlGF protein by HBO was significantly blocked by the addition of N-acetylcysteine, while wortmannin, PD98059, SP600125 and SB203580 had no effect on PlGF protein expression. However, the specific inhibitor of nitric oxide synthase, L-NAME did not alter the PlGF protein expression induced by HBO. HBO significantly increased the reactive oxygen species production and pretreatment with N-acetylcysteine significantly blocked the induction of reactive oxygen species by HBO. HBO significantly increased the migration and tube formation of MSCs and pretreatment with N-acetylcysteine and PlGF siRNA significantly blocked the induction of migration and tube formation by HBO. In conclusion, HBO induced the expression of PlGF in human bone marrow-derived MSCs at least through the oxidative stress-related pathways, which may play an important role in HBO-induced vasculogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Marrow Cells / cytology*
  • Cell Movement
  • Cells, Cultured
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • NF-E2 Transcription Factor, p45 Subunit / metabolism
  • Oxygen / pharmacology*
  • Placenta Growth Factor
  • Pregnancy Proteins / antagonists & inhibitors
  • Pregnancy Proteins / biosynthesis*
  • Pregnancy Proteins / genetics
  • Protein Biosynthesis
  • RNA Interference
  • Reactive Oxygen Species / metabolism
  • Transcription, Genetic


  • NF-E2 Transcription Factor, p45 Subunit
  • NFE2 protein, human
  • PGF protein, human
  • Pregnancy Proteins
  • Reactive Oxygen Species
  • Placenta Growth Factor
  • Oxygen