title: Treatment of pulmonary arterial hypertension with circulating angiogenic cells.
abstract: Despite advances in the treatment of pulmonary arterial hypertension, a truly restorative therapy has not been achieved. Attention has been given to circulating angiogenic cells (CACs, also termed early endothelial progenitor cells) because of their ability to home to sites of vascular injury and regenerate blood vessels. We studied the efficacy of human CAC therapy in the treatment of pulmonary arterial hypertension at two different stages of disease severity. Cells were isolated from peripheral blood and administered to nude rats on day 14 ("early") or day 21 ("late") after monocrotaline injection. The control group received monocrotaline but no cell treatment. Disease progression was assessed using right heart catheterization and echocardiography at multiple time points. Survival differences, right ventricular hypertrophy (RVH), and vascular hypertrophy were analyzed at the study endpoint. Quantitative PCR was performed to evaluate cell engraftment. Treatment with human CACs either at the early or late time points did not result in increased survival, and therapy did not prevent or reduce the severity of disease compared with control. Histological analysis of RVH and vascular muscularization showed no benefit with therapy compared with control. No detectable signal was seen of human transcript in transplanted lungs at 14 or 21 days after cell transplant. In conclusion, CAC therapy was not associated with increased survival and did not result in either clinical or histological benefits. Future studies should be geared toward either earlier therapeutic time points with varying doses of unmodified CACs or genetically modified cells as a means of delivery of factors to the pulmonary arterial circulation.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Mirsky
authors.forename: Sarah
authors.initials: S
authors.lastname: Jahn
authors.forename: Juha W
authors.initials: JW
authors.lastname: Koskenvuo
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sievers
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Yim
authors.forename: Carissa
authors.initials: C
authors.lastname: Ritner
authors.forename: Harold S
authors.initials: HS
authors.lastname: Bernstein
authors.forename: Franca S
authors.initials: FS
authors.lastname: Angeli
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Boyle
authors.forename: Teresa
authors.initials: T
authors.lastname: De Marco
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology*; D065627:Familial Primary Pulmonary Hypertension; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000628:therapy; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology / Q000628:therapy; D053208:Kaplan-Meier Estimate; D016686:Monocrotaline; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D020257:Ventricular Remodeling
chemical_list: D016686:Monocrotaline