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EnglishBACKGROUND AND AIMS: We recently demonstrated that injection of conditioned medium (CM) generated from cells of the mesenchymal region of human amniotic membrane (AMTCs) reduces bleomycin-induced lung fibrosis in mice, suggesting a crucial role of paracrine factor(s) secreted by AMTCs in these beneficial effects. We further investigated this hypothesis, the mechanisms involved, the effects on some lung functional parameters and whether AMTC-secreted effector(s) are specific to these cells and not produced by other cell types, extending the time of analysis up to 28 days after treatment. METHODS: Bleomycin-challenged mice were either treated with AMTC-CM or CM generated from human skin fibroblasts, human peripheral blood mononuclear cells or Jurkat cells, or were left untreated. Mouse lungs were analyzed for content of pro-inflammatory and pro-fibrotic molecules, presence of lymphocytes and macrophages and for fibrosis level (through histological semi-quantitative evaluation and quantitative measurement of collagen content). Arterial blood gas analysis was also performed. RESULTS: Up to 28 days after delivery, AMTC-CM-treated mice developed reduced lung fibrosis with respect to mice treated with other CM types. AMTC-CM-treated mice had comparatively better preservation of blood gas parameters and showed lower lung content of interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-1α, monocyte chemoattractant protein-1 and transforming growth factor-β associated with reduced lung macrophage levels. CONCLUSIONS: AMTC-CM prevents lung fibrosis in bleomycin-challenged mice, improving survival and preserving lung functional parameters such as blood gas exchanges. The specificity of AMTC-CM action was indicated by the absence of fibrosis reduction when other CM types were used. Finally, we provide some insights into the possible mechanisms underlying AMTC-CM-mediated control of fibrosis
Cargnoni, A., Piccinelli, E. C., Ressel, L., Rossi, D., Magatti, M., Toschi, I., Cesari, V., Albertini, M., Mazzola, S., Parolini, O., Conditioned medium from amniotic membrane-derived cells prevents lung fibrosis and preserves blood gas exchanges in bleomycin-injured mice-specificity of the effects and insights into possible mechanisms, <<CYTOTHERAPY>>, 2014; 16 (1): 17-32. [doi:10.1016/j.jcyt.2013.07.002] [http://hdl.handle.net/10807/92257]
| Autori: | ||
| Titolo: | Conditioned medium from amniotic membrane-derived cells prevents lung fibrosis and preserves blood gas exchanges in bleomycin-injured mice-specificity of the effects and insights into possible mechanisms | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.jcyt.2013.07.002 | |
| Data di pubblicazione: | 2014 | |
| Abstract: | BACKGROUND AND AIMS: We recently demonstrated that injection of conditioned medium (CM) generated from cells of the mesenchymal region of human amniotic membrane (AMTCs) reduces bleomycin-induced lung fibrosis in mice, suggesting a crucial role of paracrine factor(s) secreted by AMTCs in these beneficial effects. We further investigated this hypothesis, the mechanisms involved, the effects on some lung functional parameters and whether AMTC-secreted effector(s) are specific to these cells and not produced by other cell types, extending the time of analysis up to 28 days after treatment. METHODS: Bleomycin-challenged mice were either treated with AMTC-CM or CM generated from human skin fibroblasts, human peripheral blood mononuclear cells or Jurkat cells, or were left untreated. Mouse lungs were analyzed for content of pro-inflammatory and pro-fibrotic molecules, presence of lymphocytes and macrophages and for fibrosis level (through histological semi-quantitative evaluation and quantitative measurement of collagen content). Arterial blood gas analysis was also performed. RESULTS: Up to 28 days after delivery, AMTC-CM-treated mice developed reduced lung fibrosis with respect to mice treated with other CM types. AMTC-CM-treated mice had comparatively better preservation of blood gas parameters and showed lower lung content of interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-1α, monocyte chemoattractant protein-1 and transforming growth factor-β associated with reduced lung macrophage levels. CONCLUSIONS: AMTC-CM prevents lung fibrosis in bleomycin-challenged mice, improving survival and preserving lung functional parameters such as blood gas exchanges. The specificity of AMTC-CM action was indicated by the absence of fibrosis reduction when other CM types were used. Finally, we provide some insights into the possible mechanisms underlying AMTC-CM-mediated control of fibrosis | |
| Lingua: | Inglese | |
| Rivista: | ||
| Citazione: | Cargnoni, A., Piccinelli, E. C., Ressel, L., Rossi, D., Magatti, M., Toschi, I., Cesari, V., Albertini, M., Mazzola, S., Parolini, O., Conditioned medium from amniotic membrane-derived cells prevents lung fibrosis and preserves blood gas exchanges in bleomycin-injured mice-specificity of the effects and insights into possible mechanisms, <<CYTOTHERAPY>>, 2014; 16 (1): 17-32. [doi:10.1016/j.jcyt.2013.07.002] [http://hdl.handle.net/10807/92257] | |
| Appare nelle tipologie: | Articolo in rivista, Nota a sentenza |
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