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

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]

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

Rossi, Daniele;Parolini, Ornella
Ultimo
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
Inglese
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]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/92257
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