Somanna, Naveen K.; Woerner, Philipp M.; Murthy, Subramanyam N.; Pankey, Edward A.; Schaechtele, Deborah J.; St Hilaire, Rose-Claire; Jansen, David; Chaffin, Abigail E.; Nossaman, Bobby D.; Alt, Eckhard U.; Kadowitz, Philip J.; Izadpanah, Reza
Abstract
The effect of intratracheal administration of cyclooxygenase-1 (COX-1)-modified adipose stem cells (ASCs) on monocrotaline-induced pulmonary hypertension (MCT-PH) was investigated in the rat. The COX-1 gene was cloned from rat intestinal cells, fused with a hemagglutanin (HA) tag, and cloned into a lentiviral vector. The COX-1 lentiviral vector was shown to enhance COX-1 protein expression and inhibit proliferation of vascular smooth muscle cells without increasing apoptosis. Human ASCs transfected with the COX-1 lentiviral vector (ASC(COX-1)) display enhanced COX-1 activity while exhibiting similar differentiation potential compared with untransduced (native) ASCs. PH was induced in rats with MCT, and the rats were subsequently treated with intratracheal injection of ASC(COX-1) or untransduced ASCs. The intratracheal administration of ASC(COX-1) 3 x 10(6) cells on day 14 after MCT treatment significantly attenuated MCT-induced PH when hemodynamic values were measured on day 35 after MCT treatment whereas administration of untransduced ASCs had no significant effect. These results indicate that intratracheally administered ASC(COX-1) persisted for at least 21 days in the lung and attenuate MCT-induced PH and right ventricular hypertrophy. In addition, vasodilator responses to the nitric oxide donor sodium nitroprusside were not altered by the presence of ASC(COX-1) in the lung. These data emphasize the effectiveness of ASC(COX-1) in the treatment of experimentally induced PH.
