Abstract

Background and aimsWe 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.MethodsBleomycin-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.ResultsAt 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.ConclusionsThis pilot study supports the notion that AMTC exert anti-fibrotic effects through release of yet unknown soluble factors.

Highlights

  • Recent findings indicate compelling benefits of cellbased treatments in animal models of lung diseases associated with inflammatory and fibrotic processes [1]

  • We have reported previously that transplantation of either allogeneic or xenogeneic placental membrane-derived cells significantly reduced the severity of bleomycin-induced lung fibrosis in mice, despite a rare persistence of donor cells in the lungs of recipient animals [6]

  • We evaluated the effects of administrating conditioned medium (CM) generated from cells derived from the mesenchymal region of human amniotic membrane [11] on bleomycin-induced lung fibrosis, and observed a reduction of fibrosis progression similar to that observed previously after allogeneic and xenogeneic placental membrane-derived cell transplantation

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Summary

Introduction

Recent findings indicate compelling benefits of cellbased treatments in animal models of lung diseases associated with inflammatory and fibrotic processes [1]. Initial interest focused on the level of engraftment of transplanted cells in host lungs and their potential for regenerating lung tissue by tissue-specific differentiation, the infrequency with which either occurrence has been documented makes it likely that additional mechanisms must account for the observed improvements [1] In this regard, we have reported previously that transplantation of either allogeneic or xenogeneic placental membrane-derived cells significantly reduced the severity of bleomycin-induced lung fibrosis in mice, despite a rare persistence of donor cells in the lungs of recipient animals [6]. 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 fibrosis in this same animal model. This pilot study supports the notion that AMTC exert anti-fibrotic effects through release of yet unknown soluble factors

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