Adipose-derived stromal cell autologous transplantation ameliorates pulmonary arterial hypertension induced by shunt flow in rat models.
Hyperkinetic pulmonary arterial hypertension (PAH) severely influences the success of operation for congenital heart disease and deteriorates the prognosis of disease. Adipose-derived stromal cell (ADSC) is a good alternative multipotent stem cell for regeneration medicine. PAH rat models were established by arteriovenous shunt and ADSCs were isolated, cultured, and labeled in vitro. Twelve weeks after shunt operation, rats received an injection of 5 × 10(7) ADSCs. Two weeks after transplantation, hemodynamic abnormality induced by the shunt flow and the hypertrophy of right ventricle were reversed, which was confirmed by invasive measurement and echocardiography examination. The PAH rats receiving cell transplantation demonstrated decreased remodeling of small arteries in the lung; immunohistochemistry analysis showed augmented expression of hepatocyte growth factor (HGF) and increased number of pulmonary small arteries. Western blot and real-time reverse transcriptase-polymerase chain reaction indicated that the protein and mRNA levels of HGF and endothelial nitric oxide synthase increased, respectively, in the lung after cell transplantation. Our results suggested that ADSC transplantation can ameliorate PAH induced by shunt flow by enhancing the expression of HGF and subsequently promoting angiogenesis in the injured lung tissue.
Liu
Kai
K
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Division of Medicine, Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
Liu
Ruifang
R
Cao
Guangqing
G
Sun
Hourong
H
Wang
Xuping
X
Wu
Shuming
S
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D015153:Blotting, Western; D002454:Cell Differentiation; D048430:Cell Shape; D017690:Cell Transplantation; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D005455:Fluorescent Antibody Technique; D006439:Hemodynamics / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000097:blood; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology / Q000637:transplantation; D014182:Transplantation, Autologous; D014463:Ultrasonography
D017077:Culture Media, Conditioned; D017228:Hepatocyte Growth Factor; D052250:Nitric Oxide Synthase Type III