Abstract
Background and aims. We have demonstrated recently that transplantation of placental membrane-derived cells reduces bleomycin-induced lung fibrosis in mice, despite a limited presence of transplanted cells in host lungs. Because placenta-derived cells are known to release factors with potential immunomodulatory and trophic activities, we hypothesized that transplanted cells may promote lung tissue repair via paracrine-acting molecules. To test this hypothesis, we examined whether administration of conditioned medium (CM) generated from human amniotic mesenchymal tissue cells (AMTC) was able to reduce lung fibrosis in this same animal model. Methods. Bleomycin-challenged mice were either treated with AMTC-CM or control medium, or were left untreated (Bleo group). After 9 and 14 days, the distribution and severity of lung fibrosis were assessed histologically with a scoring system. Collagen deposition was also evaluated by quantitative image analysis. Results. At day 14, lung fibrosis scores in AMTC-CM-treated mice were significantly lower (P < 0.05) compared with mice of the Bleo group, in terms of fibrosis distribution [1.0 (interquartile range, IQR 0.9) versus 3.0 (IQR 1.8)], fibroblast proliferation [0.8 (IQR 0.4) versus 1.6 (IQR 1.0)], collagen deposition [1.4 (IQR 0.5) versus 2.0 (IQR 1.2)] and alveolar obliteration [2.3 (IQR 0.8) versus 3.2 (IQR 0.5)]. No differences were observed between mice of the Bleo group and mice treated with control medium. Quantitative analysis of collagen deposition confirmed these findings. Importantly, AMTC-CM treatment significantly reduced the fibrosis progression between the two observation time-points. Conclusions. This pilot study supports the notion that AMTC exert anti-fibrotic effects through release of yet unknown soluble factors.
Acknowledgments
We thank the physicians and midwives of the Department of Obstetrics and Gynaecology of Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy. We also thank Dr Fiammetta Adamo (IZO S.p.A, Brescia) for media lyophilization. The authors are indebted to Dr Maddalena Caruso and Dr Marco Evangelista for help in the writing and editing of the manuscript and Dr Fabio Candotti for critical revision of the manuscript.
This study was supported by a grant from Fondazione Cariplo (Bando 2004) and from MIUR (Bando FISS 2006).
A European patent application has been filed with the application number PCT2008-004845.
Disclosure of interests: No competing financial interests exist.