title: Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats.
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.
authors.affiliation: Department of Microbiology, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: Naveen K
authors.initials: NK
authors.lastname: Somanna
authors.affiliation: Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Wörner
authors.affiliation: Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: Subramanyam N
authors.initials: SN
authors.lastname: Murthy
authors.affiliation: Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pankey
authors.affiliation: Department of Microbiology, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Schächtele
authors.affiliation: Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: Rose-Claire
authors.initials: RC
authors.lastname: St Hilaire
authors.affiliation: Department of Surgery, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: David
authors.initials: D
authors.lastname: Jansen
authors.affiliation: Department of Surgery, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: Abigail E
authors.initials: AE
authors.lastname: Chaffin
authors.affiliation: Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana; Department of Anesthesiology, Critical Care Medicine Section, Ochsner Medical Center, New Orleans, Louisiana.
authors.forename: Bobby D
authors.initials: BD
authors.lastname: Nossaman
authors.affiliation: Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana; Isar Medical Center, Department of Medicine, Interdisciplinary Stem Cell Laboratory, Munich, Germany; and.
authors.forename: Eckhard U
authors.initials: EU
authors.lastname: Alt
authors.affiliation: Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana;
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
authors.affiliation: Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana; Department of Surgery, Tulane University Health Sciences Center, New Orleans, Louisiana; rizadpan@tulane.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Izadpanah
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D000818:Animals; D002454:Cell Differentiation; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics; D016686:Monocrotaline / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
chemical_list: D016686:Monocrotaline; D051545:Cyclooxygenase 1
keywords: adipose tissue-derived stem cells; bell-based therapy; cyclooxygenase-1; monocrotaline; pulmonary arterial smooth muscle cells; pulmonary hypertension