title: Autologous transplantation of bone marrow-derived endothelial progenitor cells attenuates monocrotaline-induced pulmonary arterial hypertension in rats.
abstract: OBJECTIVE
  Bone marrow-derived endothelial progenitor cells have been shown to circulate to damaged vascular endothelium and differentiate into mature endothelial cells. This study investigated whether bone marrow-derived endothelial progenitor cell therapy ameliorates monocrotaline (MCT)-induced pulmonary arterial hypertension in a rat model.
  
  
  METHODS
  Male Sprague-Dawley rats were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus autologous bone marrow-derived endothelial progenitor cell (1.2 x 10(6) cells) transplantation (group 2), and saline injection only (group 3). Mononuclear cells were obtained from femoral bone marrow of group 2 rats and isolated by Ficoll gradient centrifugation. The cells were cultured for 21 days in endothelial culture medium.
  
  
  METHODS
  An animal research laboratory at Kaohsiung Chang Gung Memorial Hospital.
  
  
  METHODS
  Hemodynamics, ventricular weight, expressions of connexin43, endothelial nitric oxide synthase messenger RNA gene, Bcl-2, and number of alveolar sacs and small lung arterioles were measured.
  
  
  RESULTS
  Hemodynamic measurements on day 28 after MCT treatment revealed the development of significantly increased pulmonary arterial hypertension in MCT-treated groups (p < .0001). The bone marrow-derived endothelial progenitor cells were intravenously transplanted in group 2 on day 28 after MCT-induced pulmonary arterial hypertension. By day 90 after MCT treatment, the right ventricular systolic blood pressure and right ventricular hypertrophy were significantly increased in group 1 compared with groups 2 and 3 (all p values <.01). In addition, connexin43 and endothelial nitric oxide synthase messenger RNA gene expressions of lung and right ventricle and Bcl-2 protein expression of right ventricle were significantly lower in group 1 than in groups 2 and 3 (all p values <.01). Furthermore, the number of alveolar sacs and small lung arterioles were significantly lower in group 1 than in groups 2 and 3 (all p values <.01).
  
  
  CONCLUSIONS
  Autologous bone marrow-derived endothelial progenitor cell transplantation effectively ameliorates MCT-induced pulmonary arterial hypertension.
authors.affiliation: Division of Cardiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Chiang-Hua
authors.initials: CH
authors.lastname: Chiang
authors.forename: Ali A
authors.initials: AA
authors.lastname: Youssef
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.forename: Chiung-Jen
authors.initials: CJ
authors.lastname: Wu
authors.forename: Morgan
authors.initials: M
authors.lastname: Fu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D042783:Endothelial Cells / Q000637:transplantation*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000601:surgery*; D008297:Male; D016686:Monocrotaline / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016686:Monocrotaline