Conditioned medium from amniotic mesenchymal tissue cells reduces progression of bleomycin-induced lung fibrosis

Background and aims. We have demonstrated recently that transplantation of placental membrane-derived cells reduces bleomycin-induced lung fi brosis in mice, despite a limited presence of transplanted cells in host lungs. Because placentaderived 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 fi brosis 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 fi brosis were assessed histologically with a scoring system. Collagen deposition was also evaluated by quantitative image analysis. Results. At day 14, lung fi brosis scores in AMTC-CM-treated mice were signifi cantly lower ( P � 0.05) compared with mice of the Bleo group, in terms of fidistribution [1.0 (interquartile range, IQR 0.9) versus 3.0 (IQR 1.8)], fi broblast 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 confi rmed these fi ndings. Importantly, AMTC-CM treatment signifi cantly reduced the fi brosis progression between the two observation time-points. Conclusions. This pilot study supports the notion that AMTC exert anti-fi brotic effects through release of yet unknown soluble factors.