Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review
The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they hav...
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| creator | McIntyre, Lauralyn A Moher, David Fergusson, Dean A Sullivan, Katrina J Mei, Shirley H J Lalu, Manoj Marshall, John Mcleod, Malcolm Griffin, Gilly Grimshaw, Jeremy Turgeon, Alexis Avey, Marc T Rudnicki, Michael A Jazi, Mazen Fishman, Jason Stewart, Duncan J |
| description | The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18-0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions. |
| doi_str_mv | 10.1371/journal.pone.0147170 |
| format | Article |
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Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18-0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0147170</identifier><identifier>PMID: 26821255</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute Lung Injury - therapy ; Adult respiratory distress syndrome ; Anesthesiology ; Animal models ; Animals ; Antibiotics ; Bacteria ; Bias ; Biology and Life Sciences ; Bone marrow ; Care and treatment ; Clinical trials ; Collaboration ; Comparative analysis ; Computational fluid dynamics ; Confidence intervals ; Critical care ; Death ; Disease Models, Animal ; Effectiveness ; Epidemiology ; Experiments ; Fatalities ; Health aspects ; Hospitals ; Humans ; Inflammation ; Injury prevention ; Lungs ; Medical ethics ; Medical treatment ; Medicine ; Medicine and Health Sciences ; Mesenchymal Stem Cell Transplantation ; Mesenchymal stem cells ; Mesenchymal Stem Cells - physiology ; Mesenchyme ; Meta-analysis ; Morbidity ; Mortality ; Physical Sciences ; Physiological aspects ; Quality assessment ; Research and Analysis Methods ; Respiratory distress syndrome ; Respiratory Distress Syndrome, Adult - therapy ; Statistical analysis ; Stem cells ; Stromal cells ; Studies ; Systematic review ; Trauma ; Treatment Outcome</subject><ispartof>PloS one, 2016-01, Vol.11 (1), p.e0147170-e0147170</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 McIntyre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2016 McIntyre et al 2016 McIntyre et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-f487228b02986fe6126b7e68b5d24087a931fc54a0cb209a9a9a092d69c8757e3</citedby><cites>FETCH-LOGICAL-c692t-f487228b02986fe6126b7e68b5d24087a931fc54a0cb209a9a9a092d69c8757e3</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/PMC4731557/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731557/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26821255$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McIntyre, Lauralyn A</creatorcontrib><creatorcontrib>Moher, David</creatorcontrib><creatorcontrib>Fergusson, Dean A</creatorcontrib><creatorcontrib>Sullivan, Katrina J</creatorcontrib><creatorcontrib>Mei, Shirley H J</creatorcontrib><creatorcontrib>Lalu, Manoj</creatorcontrib><creatorcontrib>Marshall, John</creatorcontrib><creatorcontrib>Mcleod, Malcolm</creatorcontrib><creatorcontrib>Griffin, Gilly</creatorcontrib><creatorcontrib>Grimshaw, Jeremy</creatorcontrib><creatorcontrib>Turgeon, Alexis</creatorcontrib><creatorcontrib>Avey, Marc T</creatorcontrib><creatorcontrib>Rudnicki, Michael A</creatorcontrib><creatorcontrib>Jazi, Mazen</creatorcontrib><creatorcontrib>Fishman, Jason</creatorcontrib><creatorcontrib>Stewart, Duncan J</creatorcontrib><creatorcontrib>Canadian Critical Care Translational Biology Group</creatorcontrib><title>Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18-0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.</description><subject>Acute Lung Injury - therapy</subject><subject>Adult respiratory distress syndrome</subject><subject>Anesthesiology</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Bias</subject><subject>Biology and Life Sciences</subject><subject>Bone marrow</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Collaboration</subject><subject>Comparative analysis</subject><subject>Computational fluid dynamics</subject><subject>Confidence intervals</subject><subject>Critical care</subject><subject>Death</subject><subject>Disease Models, Animal</subject><subject>Effectiveness</subject><subject>Epidemiology</subject><subject>Experiments</subject><subject>Fatalities</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Injury prevention</subject><subject>Lungs</subject><subject>Medical ethics</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - physiology</subject><subject>Mesenchyme</subject><subject>Meta-analysis</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Quality assessment</subject><subject>Research and Analysis Methods</subject><subject>Respiratory distress syndrome</subject><subject>Respiratory Distress Syndrome, Adult - therapy</subject><subject>Statistical analysis</subject><subject>Stem cells</subject><subject>Stromal cells</subject><subject>Studies</subject><subject>Systematic review</subject><subject>Trauma</subject><subject>Treatment Outcome</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1FvUyEUx2-Mxs3pNzBKYmL0oRW4XLjXB5Nmmdqky8w2fSWUe2hpKFS4d9pvL9d2y2r2YHiAwO__P4cDpyheEjwmpSAfVqGPXrnxJngYY8IEEfhRcUyako44xeXje-uj4llKK4yrsub8aXFEeU0JrarjojszxmqltygYdA4JvF5u18qhqy6GYT4F59D1EqLabJEJEU103wGa9X6Bpn7Vxy2yHn2LoJ312cmhibeD8Dy04NJHNEFX29TBWnVWo0u4sfDrefHEKJfgxX4-Kb5_Prs-_TqaXXyZnk5mI80b2o0MqwWl9RzTpuYGOKF8LoDX86qlDNdCNSUxumIK6znFjRoGbmjLG12LSkB5Urze-W5cSHJfsCSJ4AQLTgXJxHRHtEGt5CbmzONWBmXl340QF1LFnLgDWRsCYGrNOFAmKGtaU1YVLok2VLWKZq9P-2j9fA2tBt9F5Q5MD0-8XcpFuJFMlKSqRDZ4tzeI4WcPqZNrm3Suv_IQ-l3ejPMcNaNv_kEfvt2eWqh8AetNyHH1YConjBHOuKiHsOMHqDxaWFudf5exef9A8P5AkJkOfncL1ackp1eX_89e_Dhk395jl6Bct0zB9Z0NPh2CbAfqGFKKYO6KTLAcmuO2GnJoDrlvjix7df-B7kS33VD-AeH1CLo</recordid><startdate>20160128</startdate><enddate>20160128</enddate><creator>McIntyre, Lauralyn A</creator><creator>Moher, David</creator><creator>Fergusson, Dean A</creator><creator>Sullivan, Katrina J</creator><creator>Mei, Shirley H J</creator><creator>Lalu, Manoj</creator><creator>Marshall, John</creator><creator>Mcleod, Malcolm</creator><creator>Griffin, Gilly</creator><creator>Grimshaw, Jeremy</creator><creator>Turgeon, Alexis</creator><creator>Avey, Marc T</creator><creator>Rudnicki, Michael A</creator><creator>Jazi, Mazen</creator><creator>Fishman, Jason</creator><creator>Stewart, Duncan J</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>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160128</creationdate><title>Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review</title><author>McIntyre, Lauralyn A ; Moher, David ; Fergusson, Dean A ; Sullivan, Katrina J ; Mei, Shirley H J ; Lalu, Manoj ; Marshall, John ; Mcleod, Malcolm ; Griffin, Gilly ; Grimshaw, Jeremy ; Turgeon, Alexis ; Avey, Marc T ; Rudnicki, Michael A ; Jazi, Mazen ; Fishman, Jason ; Stewart, Duncan J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-f487228b02986fe6126b7e68b5d24087a931fc54a0cb209a9a9a092d69c8757e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acute Lung Injury - 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Academic</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>McIntyre, Lauralyn A</au><au>Moher, David</au><au>Fergusson, Dean A</au><au>Sullivan, Katrina J</au><au>Mei, Shirley H J</au><au>Lalu, Manoj</au><au>Marshall, John</au><au>Mcleod, Malcolm</au><au>Griffin, Gilly</au><au>Grimshaw, Jeremy</au><au>Turgeon, Alexis</au><au>Avey, Marc T</au><au>Rudnicki, Michael A</au><au>Jazi, Mazen</au><au>Fishman, Jason</au><au>Stewart, Duncan J</au><aucorp>Canadian Critical Care Translational Biology Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-01-28</date><risdate>2016</risdate><volume>11</volume><issue>1</issue><spage>e0147170</spage><epage>e0147170</epage><pages>e0147170-e0147170</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18-0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26821255</pmid><doi>10.1371/journal.pone.0147170</doi><tpages>e0147170</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-01, Vol.11 (1), p.e0147170-e0147170 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1761076271 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acute Lung Injury - therapy Adult respiratory distress syndrome Anesthesiology Animal models Animals Antibiotics Bacteria Bias Biology and Life Sciences Bone marrow Care and treatment Clinical trials Collaboration Comparative analysis Computational fluid dynamics Confidence intervals Critical care Death Disease Models, Animal Effectiveness Epidemiology Experiments Fatalities Health aspects Hospitals Humans Inflammation Injury prevention Lungs Medical ethics Medical treatment Medicine Medicine and Health Sciences Mesenchymal Stem Cell Transplantation Mesenchymal stem cells Mesenchymal Stem Cells - physiology Mesenchyme Meta-analysis Morbidity Mortality Physical Sciences Physiological aspects Quality assessment Research and Analysis Methods Respiratory distress syndrome Respiratory Distress Syndrome, Adult - therapy Statistical analysis Stem cells Stromal cells Studies Systematic review Trauma Treatment Outcome |
| title | Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review |
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