Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study
Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. St...
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| Veröffentlicht in: | PloS one 2013-08, Vol.8 (8), p.e69299 |
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| description | Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury. |
| doi_str_mv | 10.1371/journal.pone.0069299 |
| format | Article |
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Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069299</identifier><identifier>PMID: 23936322</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult Stem Cells - cytology ; Adult Stem Cells - transplantation ; Amnion ; Amnion - cytology ; Analysis ; Animal diseases ; Animal models ; Animals ; Anti-inflammatory drugs ; Biochemistry ; Biology ; Bleomycin ; Bleomycin - pharmacology ; Bone marrow ; Bone Marrow Cells - cytology ; Care and treatment ; Chronic obstructive pulmonary disease ; Collagen ; Collagen - metabolism ; Comparative studies ; Cytokines ; Disease control ; Diseases ; Drug dosages ; Epithelial cells ; Epithelial Cells - cytology ; Epithelial Cells - transplantation ; Ethics ; Female ; Fibrosis ; Gelatinase B ; Granulocyte-macrophage colony-stimulating factor ; Growth factors ; Hospitals ; Humans ; Inflammation ; Inflammation - metabolism ; Inflammation - therapy ; Inflammatory diseases ; Injection ; Injury prevention ; Interleukin 1 ; Interleukin 1 receptor antagonist ; Interleukin 1 receptors ; Interleukin 6 ; Lung diseases ; Lung Injury - chemically induced ; Lung Injury - metabolism ; Lung Injury - therapy ; Medical research ; Medical treatment ; Medicine ; Membranes ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchyme ; Mice ; Mice, Inbred C57BL ; Molecular biology ; Morbidity ; Pharmacology ; Pregnancy ; Proteins ; Receptors, Interleukin-1 - antagonists & inhibitors ; Risk factors ; Rodents ; Stem cell transplantation ; Stem cells ; Studies ; Tumor necrosis factor-α ; Womens health</subject><ispartof>PloS one, 2013-08, Vol.8 (8), p.e69299</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Moodley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Moodley et al 2013 Moodley et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-f65234d53688f0dfcdf047a1b022f323a81e37a7c15a3eb9b608748e979b9fa83</citedby><cites>FETCH-LOGICAL-c758t-f65234d53688f0dfcdf047a1b022f323a81e37a7c15a3eb9b608748e979b9fa83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731305/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731305/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23936322$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mezey, Eva</contributor><creatorcontrib>Moodley, Yuben</creatorcontrib><creatorcontrib>Vaghjiani, Vijesh</creatorcontrib><creatorcontrib>Chan, James</creatorcontrib><creatorcontrib>Baltic, Svetlana</creatorcontrib><creatorcontrib>Ryan, Marisa</creatorcontrib><creatorcontrib>Tchongue, Jorge</creatorcontrib><creatorcontrib>Samuel, Chrishan S</creatorcontrib><creatorcontrib>Murthi, Padma</creatorcontrib><creatorcontrib>Parolini, Ornella</creatorcontrib><creatorcontrib>Manuelpillai, Ursula</creatorcontrib><title>Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.</description><subject>Adult Stem Cells - cytology</subject><subject>Adult Stem Cells - transplantation</subject><subject>Amnion</subject><subject>Amnion - cytology</subject><subject>Analysis</subject><subject>Animal diseases</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anti-inflammatory drugs</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Bleomycin</subject><subject>Bleomycin - pharmacology</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - cytology</subject><subject>Care and treatment</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Collagen</subject><subject>Collagen - metabolism</subject><subject>Comparative studies</subject><subject>Cytokines</subject><subject>Disease control</subject><subject>Diseases</subject><subject>Drug dosages</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - transplantation</subject><subject>Ethics</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gelatinase B</subject><subject>Granulocyte-macrophage colony-stimulating factor</subject><subject>Growth factors</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - therapy</subject><subject>Inflammatory diseases</subject><subject>Injection</subject><subject>Injury prevention</subject><subject>Interleukin 1</subject><subject>Interleukin 1 receptor antagonist</subject><subject>Interleukin 1 receptors</subject><subject>Interleukin 6</subject><subject>Lung diseases</subject><subject>Lung Injury - chemically induced</subject><subject>Lung Injury - metabolism</subject><subject>Lung Injury - therapy</subject><subject>Medical research</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Membranes</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular biology</subject><subject>Morbidity</subject><subject>Pharmacology</subject><subject>Pregnancy</subject><subject>Proteins</subject><subject>Receptors, Interleukin-1 - antagonists & inhibitors</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Tumor necrosis factor-α</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAYhYso7jr6D0QLguBFx3w1bb0QhsWPgYUFv268CG_TZCZD2swm6eL8e7NOd5mCgs1Fy5vnnIaTk2XPMVpiWuG3Ozf6Aexy7wa1RIg3pGkeZOe4oaTgBNGHJ99n2ZMQdgiVtOb8cXZGaEM5JeQ8-7kaoinMoC30PUTnD7nSWskYcqdz6EYb8xBVn0tlbcjNkIcxRDCD6nI7Dps02Y3-8C6HXLp-Dx6iuVFJMnaHp9kjDTaoZ9N7kX3_-OHbxefi8urT-mJ1WciqrGOheUko60rK61qjTstOI1YBbhEhmhIKNVa0gkriEqhqm5ajumK1aqqmbTTUdJG9PPrurQtiyiUIzCjCvG4YScT6SHQOdmLvTQ_-IBwY8Wfg_EaAj0ZaJcpWyfR0CDBn0LGWVIQThRliNOWCktf76W9j26tOqiF6sDPT-c5gtmLjbgStKKbpChbZq8nAu-tRhfiPI0_UBtKp0gW5ZCZ7E6RYsapmJWGIJmr5FyqtTvVGpmZok-YzwZuZIDFR_YobGEMQ669f_p-9-jFnX5-wWwU2boOzYzRuCHOQHUHpXQhe6fvkMBK3xb5LQ9wWW0zFTrIXp6nfi-6aTH8D2urz2Q</recordid><startdate>20130801</startdate><enddate>20130801</enddate><creator>Moodley, Yuben</creator><creator>Vaghjiani, Vijesh</creator><creator>Chan, James</creator><creator>Baltic, Svetlana</creator><creator>Ryan, Marisa</creator><creator>Tchongue, Jorge</creator><creator>Samuel, Chrishan S</creator><creator>Murthi, Padma</creator><creator>Parolini, Ornella</creator><creator>Manuelpillai, Ursula</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130801</creationdate><title>Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study</title><author>Moodley, Yuben ; Vaghjiani, Vijesh ; Chan, James ; Baltic, Svetlana ; Ryan, Marisa ; Tchongue, Jorge ; Samuel, Chrishan S ; Murthi, Padma ; Parolini, Ornella ; Manuelpillai, Ursula</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-f65234d53688f0dfcdf047a1b022f323a81e37a7c15a3eb9b608748e979b9fa83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult Stem Cells - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moodley, Yuben</au><au>Vaghjiani, Vijesh</au><au>Chan, James</au><au>Baltic, Svetlana</au><au>Ryan, Marisa</au><au>Tchongue, Jorge</au><au>Samuel, Chrishan S</au><au>Murthi, Padma</au><au>Parolini, Ornella</au><au>Manuelpillai, Ursula</au><au>Mezey, Eva</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-08-01</date><risdate>2013</risdate><volume>8</volume><issue>8</issue><spage>e69299</spage><pages>e69299-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23936322</pmid><doi>10.1371/journal.pone.0069299</doi><tpages>e69299</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-08, Vol.8 (8), p.e69299 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1430168942 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Stem Cells - cytology Adult Stem Cells - transplantation Amnion Amnion - cytology Analysis Animal diseases Animal models Animals Anti-inflammatory drugs Biochemistry Biology Bleomycin Bleomycin - pharmacology Bone marrow Bone Marrow Cells - cytology Care and treatment Chronic obstructive pulmonary disease Collagen Collagen - metabolism Comparative studies Cytokines Disease control Diseases Drug dosages Epithelial cells Epithelial Cells - cytology Epithelial Cells - transplantation Ethics Female Fibrosis Gelatinase B Granulocyte-macrophage colony-stimulating factor Growth factors Hospitals Humans Inflammation Inflammation - metabolism Inflammation - therapy Inflammatory diseases Injection Injury prevention Interleukin 1 Interleukin 1 receptor antagonist Interleukin 1 receptors Interleukin 6 Lung diseases Lung Injury - chemically induced Lung Injury - metabolism Lung Injury - therapy Medical research Medical treatment Medicine Membranes Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchyme Mice Mice, Inbred C57BL Molecular biology Morbidity Pharmacology Pregnancy Proteins Receptors, Interleukin-1 - antagonists & inhibitors Risk factors Rodents Stem cell transplantation Stem cells Studies Tumor necrosis factor-α Womens health |
| title | Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study |
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