Autologous transplantation of bone marrow-derived endothelial progenitor cells attenuates monocrotaline-induced pulmonary arterial hypertension in rats.
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.
Yip
Hon-Kan
HK
Division of Cardiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
Chang
Li-Teh
LT
Sun
Cheuk-Kwan
CK
Sheu
Jiunn-Jye
JJ
Chiang
Chiang-Hua
CH
Youssef
Ali A
AA
Lee
Fan-Yen
FY
Wu
Chiung-Jen
CJ
Fu
Morgan
M
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
D016686:Monocrotaline