Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model

Abstract Purpose Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant mode...

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Veröffentlicht in:Journal of pediatric surgery 2014-06, Vol.49 (6), p.859-865
Hauptverfasser: Di Bernardo, Julie, Maiden, Michael M, Hershenson, Marc B, Kunisaki, Shaun M
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container_title Journal of pediatric surgery
container_volume 49
creator Di Bernardo, Julie
Maiden, Michael M
Hershenson, Marc B
Kunisaki, Shaun M
description Abstract Purpose Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Methods Pregnant Sprague–Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control ( AF - Ctr ) or nitrofen-exposed ( AF - Nitro ) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Results Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF - Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p
doi_str_mv 10.1016/j.jpedsurg.2014.01.013
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The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Methods Pregnant Sprague–Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control ( AF - Ctr ) or nitrofen-exposed ( AF - Nitro ) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Results Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF - Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p&lt;0.05). In contrast, lungs cultured in AF - Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF - Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. Conclusions AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia.</description><identifier>ISSN: 0022-3468</identifier><identifier>EISSN: 1531-5037</identifier><identifier>DOI: 10.1016/j.jpedsurg.2014.01.013</identifier><identifier>PMID: 24888823</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amniotic fluid ; Amniotic Fluid - cytology ; Animals ; Congenital diaphragmatic hernia ; Disease Models, Animal ; Female ; Fetal Development - drug effects ; Lung - drug effects ; Lung - embryology ; Lung development ; Mesenchymal stem cell ; Mesenchymal stromal cell ; Mesenchymal Stromal Cells - physiology ; Nitrofen ; Organogenesis - drug effects ; Pediatrics ; Phenyl Ethers - pharmacology ; Pregnancy ; Pregnancy, Animal ; Pulmonary hypoplasia ; Rats ; Rats, Sprague-Dawley ; Surgery</subject><ispartof>Journal of pediatric surgery, 2014-06, Vol.49 (6), p.859-865</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-ee143dfee2ab421d31cc9c8aa7e7490c22dd20e9211ac24ca08a84970a5f99a63</citedby><cites>FETCH-LOGICAL-c489t-ee143dfee2ab421d31cc9c8aa7e7490c22dd20e9211ac24ca08a84970a5f99a63</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.2014.01.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24888823$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Bernardo, Julie</creatorcontrib><creatorcontrib>Maiden, Michael M</creatorcontrib><creatorcontrib>Hershenson, Marc B</creatorcontrib><creatorcontrib>Kunisaki, Shaun M</creatorcontrib><title>Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model</title><title>Journal of pediatric surgery</title><addtitle>J Pediatr Surg</addtitle><description>Abstract Purpose Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Methods Pregnant Sprague–Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control ( AF - Ctr ) or nitrofen-exposed ( AF - Nitro ) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Results Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF - Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p&lt;0.05). In contrast, lungs cultured in AF - Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF - Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. Conclusions AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia.</description><subject>Amniotic fluid</subject><subject>Amniotic Fluid - cytology</subject><subject>Animals</subject><subject>Congenital diaphragmatic hernia</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fetal Development - drug effects</subject><subject>Lung - drug effects</subject><subject>Lung - embryology</subject><subject>Lung development</subject><subject>Mesenchymal stem cell</subject><subject>Mesenchymal stromal cell</subject><subject>Mesenchymal Stromal Cells - physiology</subject><subject>Nitrofen</subject><subject>Organogenesis - drug effects</subject><subject>Pediatrics</subject><subject>Phenyl Ethers - pharmacology</subject><subject>Pregnancy</subject><subject>Pregnancy, Animal</subject><subject>Pulmonary hypoplasia</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Surgery</subject><issn>0022-3468</issn><issn>1531-5037</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vFDEMhiMEosvCX6hy5DKLnWR3Zy6IquJLqsQBOEdp4tlmyCRLMlPYf09G23LgQmTJlvXajh8zdomwQcDdm2EzHMmVOR82AlBtAKvJJ2yFW4nNFuT-KVsBCNFItWsv2ItSBoCaBnzOLoRq6xNyxfqrMfo0ecv7MHvHHWV_T46PVCjau9NoAi9TTou3FELhZj6MFCfe01RzYY4Hfsjp13THfeSGR1_VPUVOv4_BVN2YHIWX7FlvQqFXD37Nvn94_-36U3Pz5ePn66ubxqq2mxoiVNL1RMLcKoFOorWdbY3Z0151YIVwTgB1AtFYoayB1rSq24PZ9l1ndnLNXp_7HnP6OVOZ9OjL8m8TKc1FVzp1d1SVxJrtzlKbUymZen3MfjT5pBH0wlgP-pGxXhhrwGqyFl4-zJhvR3J_yx6hVsG7s4Dqpveesi7WV5rkfCY7aZf8_2e8_aeFDT56a8IPOlEZ0pxj5ahRF6FBf10uvRx62ayGIP8AbgmnhQ</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Di Bernardo, Julie</creator><creator>Maiden, Michael M</creator><creator>Hershenson, Marc B</creator><creator>Kunisaki, Shaun M</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>20140601</creationdate><title>Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model</title><author>Di Bernardo, Julie ; Maiden, Michael M ; Hershenson, Marc B ; Kunisaki, Shaun M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-ee143dfee2ab421d31cc9c8aa7e7490c22dd20e9211ac24ca08a84970a5f99a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amniotic fluid</topic><topic>Amniotic Fluid - cytology</topic><topic>Animals</topic><topic>Congenital diaphragmatic hernia</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fetal Development - drug effects</topic><topic>Lung - drug effects</topic><topic>Lung - embryology</topic><topic>Lung development</topic><topic>Mesenchymal stem cell</topic><topic>Mesenchymal stromal cell</topic><topic>Mesenchymal Stromal Cells - physiology</topic><topic>Nitrofen</topic><topic>Organogenesis - drug effects</topic><topic>Pediatrics</topic><topic>Phenyl Ethers - pharmacology</topic><topic>Pregnancy</topic><topic>Pregnancy, Animal</topic><topic>Pulmonary hypoplasia</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di Bernardo, Julie</creatorcontrib><creatorcontrib>Maiden, Michael M</creatorcontrib><creatorcontrib>Hershenson, Marc B</creatorcontrib><creatorcontrib>Kunisaki, Shaun M</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>Di Bernardo, Julie</au><au>Maiden, Michael M</au><au>Hershenson, Marc B</au><au>Kunisaki, Shaun M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model</atitle><jtitle>Journal of pediatric surgery</jtitle><addtitle>J Pediatr Surg</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>49</volume><issue>6</issue><spage>859</spage><epage>865</epage><pages>859-865</pages><issn>0022-3468</issn><eissn>1531-5037</eissn><abstract>Abstract Purpose Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Methods Pregnant Sprague–Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control ( AF - Ctr ) or nitrofen-exposed ( AF - Nitro ) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Results Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF - Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p&lt;0.05). In contrast, lungs cultured in AF - Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF - Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. Conclusions AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24888823</pmid><doi>10.1016/j.jpedsurg.2014.01.013</doi><tpages>7</tpages></addata></record>
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subjects Amniotic fluid
Amniotic Fluid - cytology
Animals
Congenital diaphragmatic hernia
Disease Models, Animal
Female
Fetal Development - drug effects
Lung - drug effects
Lung - embryology
Lung development
Mesenchymal stem cell
Mesenchymal stromal cell
Mesenchymal Stromal Cells - physiology
Nitrofen
Organogenesis - drug effects
Pediatrics
Phenyl Ethers - pharmacology
Pregnancy
Pregnancy, Animal
Pulmonary hypoplasia
Rats
Rats, Sprague-Dawley
Surgery
title Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model
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