Combined hypothermia and mesenchymal stem cells in animal models of neonatal hypoxic–ischaemic encephalopathy: a systematic review
Background The objective of this study was to systematically review the literature to determine the effect of combined hypothermia (HTH) and mesenchymal stem cell (MSC) therapy (administered during or immediately before or after HTH) compared with HTH alone on brain injury and neurobehavioural outco...
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| Veröffentlicht in: | Pediatric research 2022-07, Vol.92 (1), p.25-31 |
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| creator | Teo, Elliot J. Jones, Lara E. Wixey, Julie A. Boyd, Roslyn N. Colditz, Paul B. Bjorkman, S. Tracey |
| description | Background
The objective of this study was to systematically review the literature to determine the effect of combined hypothermia (HTH) and mesenchymal stem cell (MSC) therapy (administered during or immediately before or after HTH) compared with HTH alone on brain injury and neurobehavioural outcomes in animal models of neonatal hypoxic–ischaemic encephalopathy.
Methods
Primary outcomes assessed were neuropathological measures and neurobehavioural measures of brain outcome. Secondary outcomes were brain protein proinflammatory cytokine status. Risk of bias (ROB) was assessed with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) ROB assessment tool.
Results
Of 393 studies identified, 3 studies in postnatal day 7 (P7) male Sprague–Dawley rats met the inclusion criteria. Meta-analyses were undertaken for neuropathological measures (apoptotic cells, astrocytes, microglia), neurobehavioral measures (rotarod test and negative geotaxis), and proinflammatory cytokine levels. Two of the three studies scored low or unclear ROB across all measures. Treatment with HTH-MSCs together significantly improved astrocyte optical density by standardised mean difference (SMD) of 0.71 [95% confidence interval (CI) −1.14, −0.28]. No other measures showed significant differences.
Conclusions
There is insufficient preclinical data to confirm the efficacy of combined HTH-MSC therapy over HTH alone. Future studies should utilise a reporting checklist such as in SYRCLE or Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve reporting standards.
Impact
Very few articles investigating the use of MSCs for the treatment of hypoxic–ischaemic encephalopathy are clinically relevant.
Continuing to publish studies in models of hypoxic–ischaemic encephalopathy without the inclusion of HTH therapy does not progress the field towards improved clinical outcomes.
This study shows that HTH and MSC therapy improves measures of astrogliosis.
More studies are required to establish the efficacy of HTH and MSCs on measures of neuropathology and neurobehavior.
The reporting of preclinical data in this space could be improved by using reporting checklists such as the SYRCLE or ARRIVE tools. |
| doi_str_mv | 10.1038/s41390-021-01716-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2569615802</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2569615802</sourcerecordid><originalsourceid>FETCH-LOGICAL-c305t-c21add112be792ca43b6cc6423c69458fe1f98c7dc274bfc8873f69e62ce1aa63</originalsourceid><addsrcrecordid>eNp9UcuO1DAQtBCIHRZ-gAOyxIVLwK_4wQ2NYEFaiQucLcfpkKziOMQZltw48Af8IV-yPcwCEgdOlqqqy11dhDzm7Dln0r4oikvHKiZ4xbjhutrukB2vJUJKmbtkx5jklXTOnpEHpVwxxlVt1X1yJpWyQhqzI9_3OTXDBC3ttzmvPSxpCDRMLU1QYIr9lsJIywqJRhjHQocJ2eEIptwCArmjE-QprAgdPb4O8ee3H0OJfYA0RIomMPdhzHNY--0lDbRsR7-wIrnAlwGuH5J7XRgLPLp9z8nHN68_7N9Wl-8v3u1fXVZRsnqtouChbTkXDRgnYlCy0TFqJWTUDpN1wDtno2mjMKrporVGdtqBFhF4CFqek2cn33nJnw9QVp9wT4wVMMGheFFrp3ltmUDp03-kV_mwTLidF4Zp5ayrHarESRWXXMoCnZ8XvM2yec78sSN_6shjR_5XR37DoSe31ocmQftn5HcpKJAnQUFq-gTL37__Y3sDqXag9g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2706498959</pqid></control><display><type>article</type><title>Combined hypothermia and mesenchymal stem cells in animal models of neonatal hypoxic–ischaemic encephalopathy: a systematic review</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Teo, Elliot J. ; Jones, Lara E. ; Wixey, Julie A. ; Boyd, Roslyn N. ; Colditz, Paul B. ; Bjorkman, S. Tracey</creator><creatorcontrib>Teo, Elliot J. ; Jones, Lara E. ; Wixey, Julie A. ; Boyd, Roslyn N. ; Colditz, Paul B. ; Bjorkman, S. Tracey</creatorcontrib><description>Background
The objective of this study was to systematically review the literature to determine the effect of combined hypothermia (HTH) and mesenchymal stem cell (MSC) therapy (administered during or immediately before or after HTH) compared with HTH alone on brain injury and neurobehavioural outcomes in animal models of neonatal hypoxic–ischaemic encephalopathy.
Methods
Primary outcomes assessed were neuropathological measures and neurobehavioural measures of brain outcome. Secondary outcomes were brain protein proinflammatory cytokine status. Risk of bias (ROB) was assessed with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) ROB assessment tool.
Results
Of 393 studies identified, 3 studies in postnatal day 7 (P7) male Sprague–Dawley rats met the inclusion criteria. Meta-analyses were undertaken for neuropathological measures (apoptotic cells, astrocytes, microglia), neurobehavioral measures (rotarod test and negative geotaxis), and proinflammatory cytokine levels. Two of the three studies scored low or unclear ROB across all measures. Treatment with HTH-MSCs together significantly improved astrocyte optical density by standardised mean difference (SMD) of 0.71 [95% confidence interval (CI) −1.14, −0.28]. No other measures showed significant differences.
Conclusions
There is insufficient preclinical data to confirm the efficacy of combined HTH-MSC therapy over HTH alone. Future studies should utilise a reporting checklist such as in SYRCLE or Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve reporting standards.
Impact
Very few articles investigating the use of MSCs for the treatment of hypoxic–ischaemic encephalopathy are clinically relevant.
Continuing to publish studies in models of hypoxic–ischaemic encephalopathy without the inclusion of HTH therapy does not progress the field towards improved clinical outcomes.
This study shows that HTH and MSC therapy improves measures of astrogliosis.
More studies are required to establish the efficacy of HTH and MSCs on measures of neuropathology and neurobehavior.
The reporting of preclinical data in this space could be improved by using reporting checklists such as the SYRCLE or ARRIVE tools.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/s41390-021-01716-y</identifier><identifier>PMID: 34482377</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animal research ; Animals ; Cytokines ; Hypothermia ; Hypoxia ; Hypoxia-Ischemia, Brain - pathology ; Hypoxia-Ischemia, Brain - therapy ; Ischemia ; Laboratory animals ; Male ; Medicine ; Medicine & Public Health ; Mesenchymal Stem Cells ; Models, Animal ; Neuropathology ; Pediatric Surgery ; Pediatrics ; Rats ; Rats, Sprague-Dawley ; Systematic Review</subject><ispartof>Pediatric research, 2022-07, Vol.92 (1), p.25-31</ispartof><rights>The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2021</rights><rights>2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.</rights><rights>The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c305t-c21add112be792ca43b6cc6423c69458fe1f98c7dc274bfc8873f69e62ce1aa63</citedby><cites>FETCH-LOGICAL-c305t-c21add112be792ca43b6cc6423c69458fe1f98c7dc274bfc8873f69e62ce1aa63</cites><orcidid>0000-0002-8491-9393</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34482377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teo, Elliot J.</creatorcontrib><creatorcontrib>Jones, Lara E.</creatorcontrib><creatorcontrib>Wixey, Julie A.</creatorcontrib><creatorcontrib>Boyd, Roslyn N.</creatorcontrib><creatorcontrib>Colditz, Paul B.</creatorcontrib><creatorcontrib>Bjorkman, S. Tracey</creatorcontrib><title>Combined hypothermia and mesenchymal stem cells in animal models of neonatal hypoxic–ischaemic encephalopathy: a systematic review</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Background
The objective of this study was to systematically review the literature to determine the effect of combined hypothermia (HTH) and mesenchymal stem cell (MSC) therapy (administered during or immediately before or after HTH) compared with HTH alone on brain injury and neurobehavioural outcomes in animal models of neonatal hypoxic–ischaemic encephalopathy.
Methods
Primary outcomes assessed were neuropathological measures and neurobehavioural measures of brain outcome. Secondary outcomes were brain protein proinflammatory cytokine status. Risk of bias (ROB) was assessed with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) ROB assessment tool.
Results
Of 393 studies identified, 3 studies in postnatal day 7 (P7) male Sprague–Dawley rats met the inclusion criteria. Meta-analyses were undertaken for neuropathological measures (apoptotic cells, astrocytes, microglia), neurobehavioral measures (rotarod test and negative geotaxis), and proinflammatory cytokine levels. Two of the three studies scored low or unclear ROB across all measures. Treatment with HTH-MSCs together significantly improved astrocyte optical density by standardised mean difference (SMD) of 0.71 [95% confidence interval (CI) −1.14, −0.28]. No other measures showed significant differences.
Conclusions
There is insufficient preclinical data to confirm the efficacy of combined HTH-MSC therapy over HTH alone. Future studies should utilise a reporting checklist such as in SYRCLE or Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve reporting standards.
Impact
Very few articles investigating the use of MSCs for the treatment of hypoxic–ischaemic encephalopathy are clinically relevant.
Continuing to publish studies in models of hypoxic–ischaemic encephalopathy without the inclusion of HTH therapy does not progress the field towards improved clinical outcomes.
This study shows that HTH and MSC therapy improves measures of astrogliosis.
More studies are required to establish the efficacy of HTH and MSCs on measures of neuropathology and neurobehavior.
The reporting of preclinical data in this space could be improved by using reporting checklists such as the SYRCLE or ARRIVE tools.</description><subject>Animal research</subject><subject>Animals</subject><subject>Cytokines</subject><subject>Hypothermia</subject><subject>Hypoxia</subject><subject>Hypoxia-Ischemia, Brain - pathology</subject><subject>Hypoxia-Ischemia, Brain - therapy</subject><subject>Ischemia</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mesenchymal Stem Cells</subject><subject>Models, Animal</subject><subject>Neuropathology</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Systematic Review</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9UcuO1DAQtBCIHRZ-gAOyxIVLwK_4wQ2NYEFaiQucLcfpkKziOMQZltw48Af8IV-yPcwCEgdOlqqqy11dhDzm7Dln0r4oikvHKiZ4xbjhutrukB2vJUJKmbtkx5jklXTOnpEHpVwxxlVt1X1yJpWyQhqzI9_3OTXDBC3ttzmvPSxpCDRMLU1QYIr9lsJIywqJRhjHQocJ2eEIptwCArmjE-QprAgdPb4O8ee3H0OJfYA0RIomMPdhzHNY--0lDbRsR7-wIrnAlwGuH5J7XRgLPLp9z8nHN68_7N9Wl-8v3u1fXVZRsnqtouChbTkXDRgnYlCy0TFqJWTUDpN1wDtno2mjMKrporVGdtqBFhF4CFqek2cn33nJnw9QVp9wT4wVMMGheFFrp3ltmUDp03-kV_mwTLidF4Zp5ayrHarESRWXXMoCnZ8XvM2yec78sSN_6shjR_5XR37DoSe31ocmQftn5HcpKJAnQUFq-gTL37__Y3sDqXag9g</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Teo, Elliot J.</creator><creator>Jones, Lara E.</creator><creator>Wixey, Julie A.</creator><creator>Boyd, Roslyn N.</creator><creator>Colditz, Paul B.</creator><creator>Bjorkman, S. Tracey</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8491-9393</orcidid></search><sort><creationdate>20220701</creationdate><title>Combined hypothermia and mesenchymal stem cells in animal models of neonatal hypoxic–ischaemic encephalopathy: a systematic review</title><author>Teo, Elliot J. ; Jones, Lara E. ; Wixey, Julie A. ; Boyd, Roslyn N. ; Colditz, Paul B. ; Bjorkman, S. Tracey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c305t-c21add112be792ca43b6cc6423c69458fe1f98c7dc274bfc8873f69e62ce1aa63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animal research</topic><topic>Animals</topic><topic>Cytokines</topic><topic>Hypothermia</topic><topic>Hypoxia</topic><topic>Hypoxia-Ischemia, Brain - pathology</topic><topic>Hypoxia-Ischemia, Brain - therapy</topic><topic>Ischemia</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mesenchymal Stem Cells</topic><topic>Models, Animal</topic><topic>Neuropathology</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Systematic Review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teo, Elliot J.</creatorcontrib><creatorcontrib>Jones, Lara E.</creatorcontrib><creatorcontrib>Wixey, Julie A.</creatorcontrib><creatorcontrib>Boyd, Roslyn N.</creatorcontrib><creatorcontrib>Colditz, Paul B.</creatorcontrib><creatorcontrib>Bjorkman, S. Tracey</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teo, Elliot J.</au><au>Jones, Lara E.</au><au>Wixey, Julie A.</au><au>Boyd, Roslyn N.</au><au>Colditz, Paul B.</au><au>Bjorkman, S. Tracey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combined hypothermia and mesenchymal stem cells in animal models of neonatal hypoxic–ischaemic encephalopathy: a systematic review</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>92</volume><issue>1</issue><spage>25</spage><epage>31</epage><pages>25-31</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><abstract>Background
The objective of this study was to systematically review the literature to determine the effect of combined hypothermia (HTH) and mesenchymal stem cell (MSC) therapy (administered during or immediately before or after HTH) compared with HTH alone on brain injury and neurobehavioural outcomes in animal models of neonatal hypoxic–ischaemic encephalopathy.
Methods
Primary outcomes assessed were neuropathological measures and neurobehavioural measures of brain outcome. Secondary outcomes were brain protein proinflammatory cytokine status. Risk of bias (ROB) was assessed with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) ROB assessment tool.
Results
Of 393 studies identified, 3 studies in postnatal day 7 (P7) male Sprague–Dawley rats met the inclusion criteria. Meta-analyses were undertaken for neuropathological measures (apoptotic cells, astrocytes, microglia), neurobehavioral measures (rotarod test and negative geotaxis), and proinflammatory cytokine levels. Two of the three studies scored low or unclear ROB across all measures. Treatment with HTH-MSCs together significantly improved astrocyte optical density by standardised mean difference (SMD) of 0.71 [95% confidence interval (CI) −1.14, −0.28]. No other measures showed significant differences.
Conclusions
There is insufficient preclinical data to confirm the efficacy of combined HTH-MSC therapy over HTH alone. Future studies should utilise a reporting checklist such as in SYRCLE or Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve reporting standards.
Impact
Very few articles investigating the use of MSCs for the treatment of hypoxic–ischaemic encephalopathy are clinically relevant.
Continuing to publish studies in models of hypoxic–ischaemic encephalopathy without the inclusion of HTH therapy does not progress the field towards improved clinical outcomes.
This study shows that HTH and MSC therapy improves measures of astrogliosis.
More studies are required to establish the efficacy of HTH and MSCs on measures of neuropathology and neurobehavior.
The reporting of preclinical data in this space could be improved by using reporting checklists such as the SYRCLE or ARRIVE tools.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>34482377</pmid><doi>10.1038/s41390-021-01716-y</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-8491-9393</orcidid></addata></record> |
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| ispartof | Pediatric research, 2022-07, Vol.92 (1), p.25-31 |
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| subjects | Animal research Animals Cytokines Hypothermia Hypoxia Hypoxia-Ischemia, Brain - pathology Hypoxia-Ischemia, Brain - therapy Ischemia Laboratory animals Male Medicine Medicine & Public Health Mesenchymal Stem Cells Models, Animal Neuropathology Pediatric Surgery Pediatrics Rats Rats, Sprague-Dawley Systematic Review |
| title | Combined hypothermia and mesenchymal stem cells in animal models of neonatal hypoxic–ischaemic encephalopathy: a systematic review |
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