Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats.
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| 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 (ASCCOX-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 ASCCOX-1 or untransduced ASCs. The intratracheal administration of ASCCOX-1 3 × 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 ASCCOX-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 ASCCOX-1 in the lung. These data emphasize the effectiveness of ASCCOX-1 in the treatment of experimentally induced PH.
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| Authors | Naveen K Somanna, Philipp M Wörner, Subramanyam N Murthy, Edward A Pankey, Deborah J Schächtele, Rose-Claire St Hilaire, David Jansen, Abigail E Chaffin, Bobby D Nossaman, Eckhard U Alt, Philip J Kadowitz, Reza Izadpanah |
| Journal | American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 307 Issue 8 Pg. H1187-95 (Oct 15 2014) ISSN: 1522-1539 [Electronic] United States |
| PMID | 25320332 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
| Copyright | Copyright © 2014 the American Physiological Society. |
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