Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats

Am J Physiol Heart Circ Physiol. 2014 Oct 15;307(8):H1187-95. doi: 10.1152/ajpheart.00589.2013. Epub 2014 Aug 22.


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.

Keywords: adipose tissue-derived stem cells; bell-based therapy; cyclooxygenase-1; monocrotaline; pulmonary arterial smooth muscle cells; pulmonary hypertension.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / cytology*
  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism*
  • Adult Stem Cells / transplantation
  • Animals
  • Cell Differentiation
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism*
  • Genetic Vectors / genetics
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / therapy*
  • Lentivirus / genetics
  • Monocrotaline / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation*


  • Monocrotaline
  • Cyclooxygenase 1