title: Effect of acute hypoxia on CXCR4 gene expression in C57BL/6 mouse bone marrow-derived mesenchymal stem cells.
abstract: BACKGROUND
  One of the most important stimuli in stem cell biology is oxygen. Chemokine receptor 4 (CXCR4) plays a crucial role in the migration and homing of stem cells. In this study, mesenchymal stem cells (MSCs) were exposed to 1% oxygen to investigate the effect of acute hypoxia on CXCR4 gene expression.
  
  
  METHODS
  MSCs were isolated from C57BL/6 mouse bone marrow and were identified and expanded in normoxic culture. Cells were incubated at 37°C under 1% hypoxic conditions for periods of 4, 8, 16, 24, and 48 h. After hypoxia preconditioning, the cells were placed in normoxic condition for 8 h to achieve cellular hypoxia-reoxygenation. To assess the level of CXCR4 gene expression, real-time quantitative reverse transcription-polymerase chain reaction was carried out for each group.
  
  
  RESULTS
  Data from statistical analysis illustrated that exposure of MSCs to acute hypoxic condition down-regulates CXCR4 expression with the maximum under-expression observed in 4 h (0.91 ± 0.107) and 8 h (50 ± 2.98) groups. Moreover, the relative gene expression of CXCR4 was decreased after hypoxia-reoxygenation by more than 80% in 4 h (0.136 ± 0.018) and 24 h (12.77 ± 0.707) groups.
  
  
  CONCLUSIONS
  The results suggest that CXCR4 expression in MSCs decreases upon acute hypoxic stress. Furthermore, hypoxia-reoxygenated MSCs showed decreased expression of CXCR4, compared to cells subjected to acute hypoxia. This difference could have resulted from the cells being compatible with low oxygen metabolism. In summary, before the therapeutic application of MSCs, it should be regarded as a necessity to optimize the oxygen concentration in these cells, as it is a critical factor in modulating CXCR4 expression.
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kadivar
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Najva
authors.initials: N
authors.lastname: Alijani
authors.affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Farahmandfar
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Saman
authors.initials: S
authors.lastname: Rahmati
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Nastaran Mohammadi
authors.initials: NM
authors.lastname: Ghahhari
authors.affiliation: Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Mahdian
keywords: CXCR4; gene expression; hypoxia; mesenchymal stem cells