Obstructive apneas induce early release of mesenchymal stem cells into circulating blood.

STUDY OBJECTIVES To investigate whether noninvasive application of recurrent airway obstructions induces early release of mesenchymal stem cells into the circulating blood in a rat model of obstructive sleep apnea. DESIGN Prospective controlled animal study. SETTING University laboratory. PATIENTS OR PARTICIPANTS Twenty male Sprague-Dawley rats (250-300 g). INTERVENTIONS A specially designed nasal mask was applied to the anesthetized rats. Ten rats were subjected to a pattern of recurrent obstructive apneas (60 per hour, lasting 15 seconds each) for 5 hours. Ten anesthetized rats were used as controls. MEASUREMENTS AND RESULTS Mesenchymal stem cells from the blood and bone marrow samples were isolated and cultured to count the total number of colony-forming unit fibroblasts (CFU-F) of adherent cells after 9 days in culture. The number of CFU-F from circulating blood was significantly (P = 0.02) higher in the rats subjected to recurrent obstructive apneas (5.00 +/- 1.16; mean +/- SEM) than in controls (1.70 +/- 0.72). No significant (P = 0.54) differences were observed in CFU-F from bone marrow. CONCLUSIONS Application of a pattern of airway obstructions similar to those experienced by patients with sleep apnea induced an early mobilization of mesenchymal stem cells into circulating blood.

[1]  D. Navajas,et al.  Collapsible upper airway segment to study the obstructive sleep apnea/hypopnea syndrome in rats , 2003, Respiratory Physiology & Neurobiology.

[2]  V. Somers,et al.  Sleep-disordered breathing and cardiovascular risk. , 2007, Sleep.

[3]  Meijing Wang,et al.  Human mesenchymal stem cells stimulated by TNF-alpha, LPS, or hypoxia produce growth factors by an NF kappa B- but not JNK-dependent mechanism. , 2008, American journal of physiology. Cell physiology.

[4]  Ramon Farré,et al.  Rat model of chronic recurrent airway obstructions to study the sleep apnea syndrome. , 2007, Sleep.

[5]  J. Ge,et al.  Temporal changes in stem cells in the circulation and myocardium of mice with Coxsackie virus B3-induced myocarditis. , 2008, Microvascular research.

[6]  R. Burt,et al.  Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. , 2008, JAMA.

[7]  N. Schork,et al.  Ventilation and metabolism among rat strains. , 1997, Journal of applied physiology.

[8]  R. Farré,et al.  Recurrent obstructive apneas trigger early systemic inflammation in a rat model of sleep apnea , 2007, Respiratory Physiology & Neurobiology.

[9]  E. Oostveen,et al.  The forced oscillation technique in clinical practice: methodology, recommendations and future developments , 2003, European Respiratory Journal.

[10]  K. Lillemoe,et al.  Mesenchymal stem cells attenuate hypoxic pulmonary vasoconstriction by a paracrine mechanism. , 2007, The Journal of surgical research.

[11]  P. Platen,et al.  Short intensive exercise increases the migratory activity of mesenchymal stem cells , 2007, British Journal of Sports Medicine.

[12]  V. Eder,et al.  Multipotential Mesenchymal Stem Cells Are Mobilized into Peripheral Blood by Hypoxia , 2006, Stem cells.

[13]  J. Bates,et al.  Comparative respiratory system mechanics in rodents. , 2000, Journal of applied physiology.

[14]  N. Nardi,et al.  Mesenchymal stem cells: isolation, in vitro expansion and characterization. , 2006 .

[15]  M. Rojas,et al.  Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. , 2007, American journal of physiology. Lung cellular and molecular physiology.