Bone Marrow, Adipose, and Lung Tissue‐Derived Murine Mesenchymal Stromal Cells Release Different Mediators and Differentially Affect Airway and Lung Parenchyma in Experimental Asthma

Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice wer...

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Veröffentlicht in:Stem cells translational medicine 2017-06, Vol.6 (6), p.1557-1567
Hauptverfasser: Abreu, Soraia C., Antunes, Mariana A., Xisto, Debora G., Cruz, Fernanda F., Branco, Vivian C., Bandeira, Elga, Zola Kitoko, Jamil, de Araújo, Almair F., Dellatorre‐Texeira, Ludmilla, Olsen, Priscilla C., Weiss, Daniel J., Diaz, Bruno L., Morales, Marcelo M., Rocco, Patricia R. M.
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container_end_page 1567
container_issue 6
container_start_page 1557
container_title Stem cells translational medicine
container_volume 6
creator Abreu, Soraia C.
Antunes, Mariana A.
Xisto, Debora G.
Cruz, Fernanda F.
Branco, Vivian C.
Bandeira, Elga
Zola Kitoko, Jamil
de Araújo, Almair F.
Dellatorre‐Texeira, Ludmilla
Olsen, Priscilla C.
Weiss, Daniel J.
Diaz, Bruno L.
Morales, Marcelo M.
Rocco, Patricia R. M.
description Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty‐four hours after the last challenge, mice received either saline (50 µl, SAL), BM‐MSCs, AD‐MSCs, or LUNG‐MSCs (105 cells per mouse in 50 µl total volume) intratracheally. At 1 week, BM‐MSCs produced significantly greater reductions in resistive and viscoelastic pressures, bronchoconstriction index, collagen fiber content in lung parenchyma (but not airways), eosinophil infiltration, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) in lung homogenates compared to AD‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung tissue. In parallel in vitro experiments, BM‐MSCs increased M2 macrophage polarization, whereas AD‐MSCs and LUNG‐MSCs had higher baseline levels of IL‐4, insulin‐like growth factor (IGF), and VEGF secretion. Exposure of MSCs to serum specimens obtained from asthmatic mice promoted reductions in secretion of these mediators, particularly in BM‐MSCs. Intratracheally administered BM‐MSCs, AD‐MSCs, and LUNG‐MSCs were differentially effective at reducing airway inflammation and remodeling and improving lung function in the current model of allergic asthma. In conclusion, intratracheal administration of MSCs from BM, AD, and LUNG were differentially effective at reducing airway inflammation and remodeling and improving lung function comparably reduced inflammation and fibrogenesis in this asthma model. However, altered lung mechanics and lung remodeling responded better to BM‐MSCs than to AD‐MSCs or LUNG‐MSCs. Moreover, each type of MSC was differentially affected in a surrogate in vitro model of the in vivo lung environment. Stem Cells Translational Medicine 2017;6:1557–1567 Bone marrow mesenchymal stromal cells (BM‐MSCs) reduced collagen fibers, eosinophils, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) compared to adipose tissue (AD)‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung, and M2 macrophage polarization. These MSCs were differentially effective at reducing airway infl
doi_str_mv 10.1002/sctm.16-0398
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M.</creator><creatorcontrib>Abreu, Soraia C. ; Antunes, Mariana A. ; Xisto, Debora G. ; Cruz, Fernanda F. ; Branco, Vivian C. ; Bandeira, Elga ; Zola Kitoko, Jamil ; de Araújo, Almair F. ; Dellatorre‐Texeira, Ludmilla ; Olsen, Priscilla C. ; Weiss, Daniel J. ; Diaz, Bruno L. ; Morales, Marcelo M. ; Rocco, Patricia R. M.</creatorcontrib><description>Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty‐four hours after the last challenge, mice received either saline (50 µl, SAL), BM‐MSCs, AD‐MSCs, or LUNG‐MSCs (105 cells per mouse in 50 µl total volume) intratracheally. At 1 week, BM‐MSCs produced significantly greater reductions in resistive and viscoelastic pressures, bronchoconstriction index, collagen fiber content in lung parenchyma (but not airways), eosinophil infiltration, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) in lung homogenates compared to AD‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung tissue. In parallel in vitro experiments, BM‐MSCs increased M2 macrophage polarization, whereas AD‐MSCs and LUNG‐MSCs had higher baseline levels of IL‐4, insulin‐like growth factor (IGF), and VEGF secretion. Exposure of MSCs to serum specimens obtained from asthmatic mice promoted reductions in secretion of these mediators, particularly in BM‐MSCs. Intratracheally administered BM‐MSCs, AD‐MSCs, and LUNG‐MSCs were differentially effective at reducing airway inflammation and remodeling and improving lung function in the current model of allergic asthma. In conclusion, intratracheal administration of MSCs from BM, AD, and LUNG were differentially effective at reducing airway inflammation and remodeling and improving lung function comparably reduced inflammation and fibrogenesis in this asthma model. However, altered lung mechanics and lung remodeling responded better to BM‐MSCs than to AD‐MSCs or LUNG‐MSCs. Moreover, each type of MSC was differentially affected in a surrogate in vitro model of the in vivo lung environment. Stem Cells Translational Medicine 2017;6:1557–1567 Bone marrow mesenchymal stromal cells (BM‐MSCs) reduced collagen fibers, eosinophils, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) compared to adipose tissue (AD)‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung, and M2 macrophage polarization. These MSCs were differentially effective at reducing airway inflammation and remodeling in allergic asthma.</description><identifier>ISSN: 2157-6564</identifier><identifier>ISSN: 2157-6580</identifier><identifier>EISSN: 2157-6580</identifier><identifier>DOI: 10.1002/sctm.16-0398</identifier><identifier>PMID: 28425576</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adipose Stem Cells/VSF ; Adipose tissue ; Advertising executives ; Analysis ; Angiogenesis ; Antibiotics ; Asthma ; Biomarkers ; Bone marrow ; Bone Marrow Stem Cells ; Bronchoconstriction ; Collagen ; Cytokines ; Disease Models (Animal/Cell) ; Ethylenediaminetetraacetic acid ; Experiments ; Fibrosis ; Growth factors ; Inflammation ; Inflammation / Inflammatory Disease ; Insulin ; Insulin-like growth factors ; Interferon ; Laboratory animals ; Leukocytes (eosinophilic) ; Lungs ; Macrophage ; Macrophages ; Mesenchymal Stem Cells ; Mesenchymal stromal cells ; Mesenchyme ; Ovalbumin ; Parenchyma ; Research funding ; Respiratory function ; Respiratory tract ; Respiratory tract diseases ; Stem cell transplantation ; Stem cells ; Stromal cells ; Studies ; Tissue Engineering and Regenerative Medicine ; Trachea ; Transforming growth factor ; Transforming growth factors ; Translational s and Reviews ; Vascular endothelial growth factor ; Viscoelasticity</subject><ispartof>Stem cells translational medicine, 2017-06, Vol.6 (6), p.1557-1567</ispartof><rights>2017 The Authors published by Wiley Periodicals, Inc. on behalf of AlphaMed Press</rights><rights>2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.</rights><rights>COPYRIGHT 2017 Oxford University Press</rights><rights>2017. 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M.</creatorcontrib><title>Bone Marrow, Adipose, and Lung Tissue‐Derived Murine Mesenchymal Stromal Cells Release Different Mediators and Differentially Affect Airway and Lung Parenchyma in Experimental Asthma</title><title>Stem cells translational medicine</title><addtitle>Stem Cells Transl Med</addtitle><description>Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty‐four hours after the last challenge, mice received either saline (50 µl, SAL), BM‐MSCs, AD‐MSCs, or LUNG‐MSCs (105 cells per mouse in 50 µl total volume) intratracheally. At 1 week, BM‐MSCs produced significantly greater reductions in resistive and viscoelastic pressures, bronchoconstriction index, collagen fiber content in lung parenchyma (but not airways), eosinophil infiltration, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) in lung homogenates compared to AD‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung tissue. In parallel in vitro experiments, BM‐MSCs increased M2 macrophage polarization, whereas AD‐MSCs and LUNG‐MSCs had higher baseline levels of IL‐4, insulin‐like growth factor (IGF), and VEGF secretion. Exposure of MSCs to serum specimens obtained from asthmatic mice promoted reductions in secretion of these mediators, particularly in BM‐MSCs. Intratracheally administered BM‐MSCs, AD‐MSCs, and LUNG‐MSCs were differentially effective at reducing airway inflammation and remodeling and improving lung function in the current model of allergic asthma. In conclusion, intratracheal administration of MSCs from BM, AD, and LUNG were differentially effective at reducing airway inflammation and remodeling and improving lung function comparably reduced inflammation and fibrogenesis in this asthma model. However, altered lung mechanics and lung remodeling responded better to BM‐MSCs than to AD‐MSCs or LUNG‐MSCs. Moreover, each type of MSC was differentially affected in a surrogate in vitro model of the in vivo lung environment. Stem Cells Translational Medicine 2017;6:1557–1567 Bone marrow mesenchymal stromal cells (BM‐MSCs) reduced collagen fibers, eosinophils, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) compared to adipose tissue (AD)‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung, and M2 macrophage polarization. These MSCs were differentially effective at reducing airway inflammation and remodeling in allergic asthma.</description><subject>Adipose Stem Cells/VSF</subject><subject>Adipose tissue</subject><subject>Advertising executives</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Antibiotics</subject><subject>Asthma</subject><subject>Biomarkers</subject><subject>Bone marrow</subject><subject>Bone Marrow Stem Cells</subject><subject>Bronchoconstriction</subject><subject>Collagen</subject><subject>Cytokines</subject><subject>Disease Models (Animal/Cell)</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Experiments</subject><subject>Fibrosis</subject><subject>Growth factors</subject><subject>Inflammation</subject><subject>Inflammation / Inflammatory Disease</subject><subject>Insulin</subject><subject>Insulin-like growth factors</subject><subject>Interferon</subject><subject>Laboratory animals</subject><subject>Leukocytes (eosinophilic)</subject><subject>Lungs</subject><subject>Macrophage</subject><subject>Macrophages</subject><subject>Mesenchymal Stem Cells</subject><subject>Mesenchymal stromal cells</subject><subject>Mesenchyme</subject><subject>Ovalbumin</subject><subject>Parenchyma</subject><subject>Research funding</subject><subject>Respiratory function</subject><subject>Respiratory tract</subject><subject>Respiratory tract diseases</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stromal cells</subject><subject>Studies</subject><subject>Tissue Engineering and Regenerative Medicine</subject><subject>Trachea</subject><subject>Transforming growth factor</subject><subject>Transforming growth factors</subject><subject>Translational s and Reviews</subject><subject>Vascular endothelial growth factor</subject><subject>Viscoelasticity</subject><issn>2157-6564</issn><issn>2157-6580</issn><issn>2157-6580</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kstu1DAUhiMEolXpjjWyxIbFpPgSO_YGKUzLRZoKRIe15SYnM66SeGonHbLjEXgcnocnwWGGKbDAm-PLd_5zjvUnyVOCzwjG9GUo-_aMiBQzJR8kx5TwPBVc4oeHvciOktMQbnBcQglF8ePkiMqMcp6L4-T7a9cBujTeu-0MFZXduAAzZLoKLYZuhZY2hAF-fP12Dt7eQYUuB2-nDAjQleuxNQ266r2b4hyaJqBP0IAJgM5tXYOHro9sZU3vfPgle7i3pmlGVMRT2aPC-q0Z7-t-NH6vj2yHLr5sYvk2JsUyRejXrXmSPKpNE-B0H0-Sz28ulvN36eLD2_fzYpGWnGORQplLVSkjgRKDuaI1lobHGyYrgQFXFQFOeabYtYlnpqqIm1qVuIYMIGMnyaud7ma4bqEqYw_eNHoT2zF-1M5Y_fdLZ9d65e40F1LlgkaBF3sB724HCL1ubSjjV5kO3BA0kYpgqTI2oc__QW_c4Ls4nqZUKiE4Y_ieWpkGtO1qF-uWk6gucsbzHGdKRmq2o0rvQvBQH1omWE_e0ZN3NBF68k7En_055gH-7ZQIsB2wtQ2M_xXTV_MlI9F_gv0EnL_TWA</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Abreu, Soraia C.</creator><creator>Antunes, Mariana A.</creator><creator>Xisto, Debora G.</creator><creator>Cruz, Fernanda F.</creator><creator>Branco, Vivian C.</creator><creator>Bandeira, Elga</creator><creator>Zola Kitoko, Jamil</creator><creator>de Araújo, Almair F.</creator><creator>Dellatorre‐Texeira, Ludmilla</creator><creator>Olsen, Priscilla C.</creator><creator>Weiss, Daniel J.</creator><creator>Diaz, Bruno L.</creator><creator>Morales, Marcelo M.</creator><creator>Rocco, Patricia R. 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M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone Marrow, Adipose, and Lung Tissue‐Derived Murine Mesenchymal Stromal Cells Release Different Mediators and Differentially Affect Airway and Lung Parenchyma in Experimental Asthma</atitle><jtitle>Stem cells translational medicine</jtitle><addtitle>Stem Cells Transl Med</addtitle><date>2017-06</date><risdate>2017</risdate><volume>6</volume><issue>6</issue><spage>1557</spage><epage>1567</epage><pages>1557-1567</pages><issn>2157-6564</issn><issn>2157-6580</issn><eissn>2157-6580</eissn><abstract>Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty‐four hours after the last challenge, mice received either saline (50 µl, SAL), BM‐MSCs, AD‐MSCs, or LUNG‐MSCs (105 cells per mouse in 50 µl total volume) intratracheally. At 1 week, BM‐MSCs produced significantly greater reductions in resistive and viscoelastic pressures, bronchoconstriction index, collagen fiber content in lung parenchyma (but not airways), eosinophil infiltration, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) in lung homogenates compared to AD‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung tissue. In parallel in vitro experiments, BM‐MSCs increased M2 macrophage polarization, whereas AD‐MSCs and LUNG‐MSCs had higher baseline levels of IL‐4, insulin‐like growth factor (IGF), and VEGF secretion. Exposure of MSCs to serum specimens obtained from asthmatic mice promoted reductions in secretion of these mediators, particularly in BM‐MSCs. Intratracheally administered BM‐MSCs, AD‐MSCs, and LUNG‐MSCs were differentially effective at reducing airway inflammation and remodeling and improving lung function in the current model of allergic asthma. In conclusion, intratracheal administration of MSCs from BM, AD, and LUNG were differentially effective at reducing airway inflammation and remodeling and improving lung function comparably reduced inflammation and fibrogenesis in this asthma model. However, altered lung mechanics and lung remodeling responded better to BM‐MSCs than to AD‐MSCs or LUNG‐MSCs. Moreover, each type of MSC was differentially affected in a surrogate in vitro model of the in vivo lung environment. Stem Cells Translational Medicine 2017;6:1557–1567 Bone marrow mesenchymal stromal cells (BM‐MSCs) reduced collagen fibers, eosinophils, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) compared to adipose tissue (AD)‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung, and M2 macrophage polarization. These MSCs were differentially effective at reducing airway inflammation and remodeling in allergic asthma.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>28425576</pmid><doi>10.1002/sctm.16-0398</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1412-7136</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adipose Stem Cells/VSF
Adipose tissue
Advertising executives
Analysis
Angiogenesis
Antibiotics
Asthma
Biomarkers
Bone marrow
Bone Marrow Stem Cells
Bronchoconstriction
Collagen
Cytokines
Disease Models (Animal/Cell)
Ethylenediaminetetraacetic acid
Experiments
Fibrosis
Growth factors
Inflammation
Inflammation / Inflammatory Disease
Insulin
Insulin-like growth factors
Interferon
Laboratory animals
Leukocytes (eosinophilic)
Lungs
Macrophage
Macrophages
Mesenchymal Stem Cells
Mesenchymal stromal cells
Mesenchyme
Ovalbumin
Parenchyma
Research funding
Respiratory function
Respiratory tract
Respiratory tract diseases
Stem cell transplantation
Stem cells
Stromal cells
Studies
Tissue Engineering and Regenerative Medicine
Trachea
Transforming growth factor
Transforming growth factors
Translational s and Reviews
Vascular endothelial growth factor
Viscoelasticity
title Bone Marrow, Adipose, and Lung Tissue‐Derived Murine Mesenchymal Stromal Cells Release Different Mediators and Differentially Affect Airway and Lung Parenchyma in Experimental Asthma
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