Rat Model Of Emphysema Research Articles

Autologous Transplantation of Adipose Tissue-Derived Stromal Cells Ameliorates Pulmonary Emphysema

Adipose tissue is a useful tool for management of most complex cardiothoracic problems, including the reinforcement of damaged lungs, and adipose tissue-derived stromal cells (ASCs) have been suggested to secrete hepatocyte growth factor (HGF), a multipotent regenerative factor that contributes to the repair process after lung injury. The goal of this study was to demonstrate the therapeutic impact of autologous transplantation of ASCs through HGF supplementation for the enhancement of alveolar repair in a rat model of emphysema. ASCs were isolated from inguinal subcutaneous fat pads and characterized by flow cytometry. Cultured ASC were found to secrete significantly larger amounts of HGF (15 112 +/- 1628 pg per 10(6) cells) than other angiogenic factors. Transplantation of ASCs into elastase-treated emphysema models induced a significant increase in endogenous HGF expression in lung tissues with a small amount of increase in other organs, with the high levels lasting for up to 4 weeks after transplantation. Further, alveolar and vascular regeneration were significantly enhanced via inhibition of alveolar cell apoptosis, enhancement of epithelial cell proliferation and promotion of angiogenesis in pulmonary vasculature, leading to restoration of pulmonary function affected by emphysema. These data suggest that autologous ASC cell therapy may have a therapeutic potential for pulmonary emphysema, through inducing HGF expression selectively in injured lung tissues.

Lung Tissue Engineering Technique with Adipose Stromal Cells Improves Surgical Outcome for Pulmonary Emphysema

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. 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. 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.

Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treatment.

We investigated the relationship between the microscopic elastic and hysteretic behavior of the alveolar walls and the macroscopic mechanical properties of the whole lung in an in vivo elastase-treated rat model of emphysema. We measured the input impedance of isolated lungs at three levels of transpulmonary pressure (Ptp) and used a linear model to estimate the dynamic elastance and hysteresivity of the lungs. The elastance of the normal lungs increased steeply with Ptp, whereas this dependence diminished in the treated lungs. Hysteresivity decreased significantly with Ptp in the normal lungs, but this dependence disappeared in the treated lungs. To investigate the microscopic origins of these changes, the alveolar walls were immunofluorescently labeled in small tissue strips. By using a fluorescent microscope, the lengths and angular orientations of individual alveolar walls were followed during cyclic uniaxial stretching of the tissue strips. The microstrains (relative change in segment length) and changes in angle of the alveolar walls showed considerable heterogeneity, which was interpreted in terms of a network model. In the normal strips, the alveolar walls showed larger angular changes compared with the treated tissue, whereas the alveolar walls of the treated tissue tended to be more extensible. Hysteresis in the average angle change was also larger in the treated tissue than in the normal tissue. We conclude that the decreased Ptp dependence of elastance and the constant hysteresivity in the treated lungs are related to microstructural remodeling and network phenomena at the level of the alveolar walls.

MRNA expression of basic fibroblast growth factor from a single intratracheal instillation of papain-induced emphysema in rats.

The relations between mRNA expression of basic fibroblast growth factor (bFGF) and the changes in collagen I and collagen III in pulmonary tissues from a single intratracheal instillation of papain-induced emphysema in rats were investigated. Wistar rats (n = 42) were randomly divided into normal group and emphysema model 1, 3, 5, 7, 15, 30-day groups (n = 6 in each group). The rat model of emphysema was induced by a single intratracheal instillation of papain. The results of immunohistochemistry SABC and in situ hybridization with bFGF probe were quantitatively analyzed to examine the changes of collagen I and collagen III and bFGF mRNA expression in lung tissues and the percent of positive expression of bFGFmRNA in alveolar macrophages. The results were as follows: (1) In the emphysema model groups the optical densities of collagen I and collagen III began to increase after 3 days, reached the highest at the 7th day, and began to reduce at the 15th day; (2) No expression of bFGFmRNA in pulmonary tissues was detectable in the normal group. The positive expression of bFGFmRNA was detectable in lung tissues one day after the intratracheal instillation of papain. The average optical densities reached the peak (41.895 +/- 7.017) at the 7th day, significantly higher than in the normal group (0.581 +/- 0.139, P < 0.01). The positive expression of bFGFmRNA in lung tissues began to reduce at the 15th day; (3) Positive expression of bFGFmRNA in alveolar macrophages of instillation papain rats was detectable 3 days after the intratracheal instillation of papain, and reached the highest at the 7th day with the percent of positive expression of bFGF mRNA in alveolar macrophages being 70.13 +/- 11.21, higher than in the normal group (5.12 +/- 0.18, P < 0.01); (4) The expression of bFGF mRNA in the lung tissues and macrophages was positively related with the changes in collagen I and collagen III (P < 0.01 or P < 0.05) respectively. It was suggested that the up-regulation of bFGF mRNA expression during the development of emphysema can lead pulmonary interstitial fibrosis, which may take part in the injury and repair and the lung tissue reconstruction.