Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis

Abstract Purpose We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis. Methods Rat fetuses (n = 117) with surgically created gastroschisis were divided into three grou...

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Veröffentlicht in:Journal of pediatric surgery 2016-01, Vol.51 (1), p.56-61
Hauptverfasser: Feng, Christina, Graham, Christopher D, Connors, John Patrick, Brazzo, Joseph, Pan, Amy H.S, Hamilton, James R, Zurakowski, David, Fauza, Dario O
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container_end_page 61
container_issue 1
container_start_page 56
container_title Journal of pediatric surgery
container_volume 51
creator Feng, Christina
Graham, Christopher D
Connors, John Patrick
Brazzo, Joseph
Pan, Amy H.S
Hamilton, James R
Zurakowski, David
Fauza, Dario O
description Abstract Purpose We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis. Methods Rat fetuses (n = 117) with surgically created gastroschisis were divided into three groups: untreated animals (n = 62) and two groups receiving volume-matched intraamniotic injections of either saline (n = 25) or 2 × 106 cells/mL of syngeneic, labeled afMSCs (n = 30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P < 0.05). Results Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P = 0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P = 0.003/0.05/< 0.001/0.026, respectively). There were no such significant differences between the untreated and saline groups. There were no differences between the afMSC group and NL, except for a significantly thicker muscular layer in the afMSC group (P = 0.014). Labeled afMSCs were scarcely identified, suggesting a paracrine effect. Conclusions Amniotic mesenchymal stem cells mitigate bowel damage in experimental gastroschisis after concentrated intraamniotic injection. Transamniotic stem cell therapy (TRASCET) may become a practical component of the treatment of gastroschisis.
doi_str_mv 10.1016/j.jpedsurg.2015.10.011
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Methods Rat fetuses (n = 117) with surgically created gastroschisis were divided into three groups: untreated animals (n = 62) and two groups receiving volume-matched intraamniotic injections of either saline (n = 25) or 2 × 106 cells/mL of syngeneic, labeled afMSCs (n = 30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P &lt; 0.05). Results Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P = 0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P = 0.003/0.05/&lt; 0.001/0.026, respectively). There were no such significant differences between the untreated and saline groups. There were no differences between the afMSC group and NL, except for a significantly thicker muscular layer in the afMSC group (P = 0.014). Labeled afMSCs were scarcely identified, suggesting a paracrine effect. Conclusions Amniotic mesenchymal stem cells mitigate bowel damage in experimental gastroschisis after concentrated intraamniotic injection. Transamniotic stem cell therapy (TRASCET) may become a practical component of the treatment of gastroschisis.</description><identifier>ISSN: 0022-3468</identifier><identifier>EISSN: 1531-5037</identifier><identifier>DOI: 10.1016/j.jpedsurg.2015.10.011</identifier><identifier>PMID: 26548631</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amnion ; Amniotic Fluid - cytology ; Amniotic mesenchymal stem cells ; Animals ; Female ; Fetal stem cells ; Fetal Therapies - methods ; Fetal therapy ; Gastroschisis ; Gastroschisis - pathology ; Gastroschisis - therapy ; Injections ; Intestines - pathology ; Mesenchymal Stem Cell Transplantation - methods ; Pediatrics ; Rats ; Rats, Sprague-Dawley ; Regenerative medicine ; Surgery ; Treatment Outcome</subject><ispartof>Journal of pediatric surgery, 2016-01, Vol.51 (1), p.56-61</ispartof><rights>Elsevier Inc.</rights><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-bf0ed7432661db518482ff1545582dfeefc20ad6edd5880f1297f1c4d9580f843</citedby><cites>FETCH-LOGICAL-c493t-bf0ed7432661db518482ff1545582dfeefc20ad6edd5880f1297f1c4d9580f843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jpedsurg.2015.10.011$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26548631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Christina</creatorcontrib><creatorcontrib>Graham, Christopher D</creatorcontrib><creatorcontrib>Connors, John Patrick</creatorcontrib><creatorcontrib>Brazzo, Joseph</creatorcontrib><creatorcontrib>Pan, Amy H.S</creatorcontrib><creatorcontrib>Hamilton, James R</creatorcontrib><creatorcontrib>Zurakowski, David</creatorcontrib><creatorcontrib>Fauza, Dario O</creatorcontrib><title>Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis</title><title>Journal of pediatric surgery</title><addtitle>J Pediatr Surg</addtitle><description>Abstract Purpose We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis. Methods Rat fetuses (n = 117) with surgically created gastroschisis were divided into three groups: untreated animals (n = 62) and two groups receiving volume-matched intraamniotic injections of either saline (n = 25) or 2 × 106 cells/mL of syngeneic, labeled afMSCs (n = 30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P &lt; 0.05). Results Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P = 0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P = 0.003/0.05/&lt; 0.001/0.026, respectively). There were no such significant differences between the untreated and saline groups. There were no differences between the afMSC group and NL, except for a significantly thicker muscular layer in the afMSC group (P = 0.014). Labeled afMSCs were scarcely identified, suggesting a paracrine effect. Conclusions Amniotic mesenchymal stem cells mitigate bowel damage in experimental gastroschisis after concentrated intraamniotic injection. Transamniotic stem cell therapy (TRASCET) may become a practical component of the treatment of gastroschisis.</description><subject>Amnion</subject><subject>Amniotic Fluid - cytology</subject><subject>Amniotic mesenchymal stem cells</subject><subject>Animals</subject><subject>Female</subject><subject>Fetal stem cells</subject><subject>Fetal Therapies - methods</subject><subject>Fetal therapy</subject><subject>Gastroschisis</subject><subject>Gastroschisis - pathology</subject><subject>Gastroschisis - therapy</subject><subject>Injections</subject><subject>Intestines - pathology</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Pediatrics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Regenerative medicine</subject><subject>Surgery</subject><subject>Treatment Outcome</subject><issn>0022-3468</issn><issn>1531-5037</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvEzEUhS0EoqHwFyovy2LCvZ6xM9kgqqhApUpINEgskCzHvk49zCPYM1T593iUlgUbVpaPzn2c7zJ2gbBEQPWuWTYHcmmK-6UAlFlcAuIztkBZYiGhXD1nCwAhirJS9Rl7lVIDkGXAl-xMKFnVqsQF-7GNpk-m68MwBsvTSB231LZ8vKdoDkd-uf16dbe53r7lXRjD3oyU-G54oJY705k98dBzw7vBZWXwfG_SGIdk70MK6TV74U2b6M3je86-fbzebj4Xt18-3Wyubgtbrcux2Hkgt6pKoRS6ncS6qoX3KCspa-E8kbcCjFPknKxr8CjWK4-2cmuZf3VVnrPLU99DHH5NlEbdhTSnMD0NU9K4UlDn5EJmqzpZbd4yRfL6EENn4lEj6JmsbvQTWT2TnfVMNhdePM6Ydh25v2VPKLPhw8lAOenvQFEnG6i35EIkO2o3hP_PeP9PC9uGPljT_qQjpWaYYp85atRJaNB3833n86IEUAK-l38AFnOiHw</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Feng, Christina</creator><creator>Graham, Christopher D</creator><creator>Connors, John Patrick</creator><creator>Brazzo, Joseph</creator><creator>Pan, Amy H.S</creator><creator>Hamilton, James R</creator><creator>Zurakowski, David</creator><creator>Fauza, Dario O</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20160101</creationdate><title>Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis</title><author>Feng, Christina ; Graham, Christopher D ; Connors, John Patrick ; Brazzo, Joseph ; Pan, Amy H.S ; Hamilton, James R ; Zurakowski, David ; Fauza, Dario O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-bf0ed7432661db518482ff1545582dfeefc20ad6edd5880f1297f1c4d9580f843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amnion</topic><topic>Amniotic Fluid - cytology</topic><topic>Amniotic mesenchymal stem cells</topic><topic>Animals</topic><topic>Female</topic><topic>Fetal stem cells</topic><topic>Fetal Therapies - methods</topic><topic>Fetal therapy</topic><topic>Gastroschisis</topic><topic>Gastroschisis - pathology</topic><topic>Gastroschisis - therapy</topic><topic>Injections</topic><topic>Intestines - pathology</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Pediatrics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Regenerative medicine</topic><topic>Surgery</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Christina</creatorcontrib><creatorcontrib>Graham, Christopher D</creatorcontrib><creatorcontrib>Connors, John Patrick</creatorcontrib><creatorcontrib>Brazzo, Joseph</creatorcontrib><creatorcontrib>Pan, Amy H.S</creatorcontrib><creatorcontrib>Hamilton, James R</creatorcontrib><creatorcontrib>Zurakowski, David</creatorcontrib><creatorcontrib>Fauza, Dario O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pediatric surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Christina</au><au>Graham, Christopher D</au><au>Connors, John Patrick</au><au>Brazzo, Joseph</au><au>Pan, Amy H.S</au><au>Hamilton, James R</au><au>Zurakowski, David</au><au>Fauza, Dario O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis</atitle><jtitle>Journal of pediatric surgery</jtitle><addtitle>J Pediatr Surg</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>51</volume><issue>1</issue><spage>56</spage><epage>61</epage><pages>56-61</pages><issn>0022-3468</issn><eissn>1531-5037</eissn><abstract>Abstract Purpose We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis. Methods Rat fetuses (n = 117) with surgically created gastroschisis were divided into three groups: untreated animals (n = 62) and two groups receiving volume-matched intraamniotic injections of either saline (n = 25) or 2 × 106 cells/mL of syngeneic, labeled afMSCs (n = 30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P &lt; 0.05). Results Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P = 0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P = 0.003/0.05/&lt; 0.001/0.026, respectively). There were no such significant differences between the untreated and saline groups. There were no differences between the afMSC group and NL, except for a significantly thicker muscular layer in the afMSC group (P = 0.014). Labeled afMSCs were scarcely identified, suggesting a paracrine effect. Conclusions Amniotic mesenchymal stem cells mitigate bowel damage in experimental gastroschisis after concentrated intraamniotic injection. Transamniotic stem cell therapy (TRASCET) may become a practical component of the treatment of gastroschisis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26548631</pmid><doi>10.1016/j.jpedsurg.2015.10.011</doi><tpages>6</tpages></addata></record>
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subjects Amnion
Amniotic Fluid - cytology
Amniotic mesenchymal stem cells
Animals
Female
Fetal stem cells
Fetal Therapies - methods
Fetal therapy
Gastroschisis
Gastroschisis - pathology
Gastroschisis - therapy
Injections
Intestines - pathology
Mesenchymal Stem Cell Transplantation - methods
Pediatrics
Rats
Rats, Sprague-Dawley
Regenerative medicine
Surgery
Treatment Outcome
title Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis
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