Lung tissue engineering technique with adipose stromal cells improves surgical outcome for pulmonary emphysema.
OBJECTIVE
Hepatocyte growth factor (HGF) is a potent regenerative factor generated after a lung injury, and HGF supplementation after surgical reduction has been shown to enhance compensatory growth in remnant lungs and improve pathophysiologic conditions in a rat model of emphysema. Adipose tissue-derived stromal cells (ASCs) produce a large amount of angiogenic factors, including HGF. After lung volume reduction surgery (LVRS), we treated rats by implanting HGF-secreting ASCs with a scaffold onto the remnant lung tissue to determine the usefulness of this technique for treating respiratory dysfunction.


RESULTS
Cells were isolated from rat inguinal adipose tissue and characterized by flow cytometry. ASCs were cultured on a polyglycolic acid felt sheet as a sealant material, and were shown to secrete significantly greater amounts of HGF than other angiogenic factors. Next, ASCs on polyglycolic acid felt sheets were used to cover the cut edge of the remaining lungs after LVRS for emphysema in rats. One week after implantation of the ASCs, both alveolar and vascular regeneration were significantly accelerated as compared with the rats that underwent LVRS alone. Consequently, gas exchange and exercise tolerance were also significantly restored, with these good results persisting for more than 1 mo.


CONCLUSIONS
The present findings demonstrate the therapeutic potential of cell therapy using ASCs with a scaffold for selective delivery of HGF to remnant lungs, which resulted in enhancement of compensatory growth, after surgical resection. This approach may provide a new strategy for lung tissue engineering to improve LVRS outcome.
Shigemura
Norihisa
N
Division of Cardiothoracic Surgery, Department of Surgery, Course of Advanced Medicine, Medical Center for Translational Research, Osaka University Graduate School of Medicine, Osaka, Japan.
Okumura
Meinoshin
M
Mizuno
Shinya
S
Imanishi
Yukiko
Y
Matsuyama
Akifumi
A
Shiono
Hiroyuki
H
Nakamura
Toshikazu
T
Sawa
Yoshiki
Y
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D011013:Pneumonectomy; D011650:Pulmonary Alveoli / Q000502:physiology; D011656:Pulmonary Emphysema / Q000601:surgery*; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000502:physiology; D012129:Respiratory Function Tests; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*
D017077:Culture Media, Conditioned; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor