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Thus, modulation of the maternal intrauterine environment may be a key therapeutic avenue to prevent preeclampsia-associated developmental lung injury. A biologic therapy of interest is mesenchymal stromal cell\u2013derived extracellular vesicles (MEx), which we have previously shown to ameliorate preeclamptic physiology through intrauterine immunomodulation. To evaluate the therapeutic potential of MEx to improve developmental lung injury in experimental preeclampsia, using the heme oxygenase-1\u2013null mouse (Hmox1\u2212 \u00a0\/\u2212) model, preeclamptic pregnant dams were administered intravenous antenatal MEx treatment during each week of pregnancy followed by analysis of fetal and postnatal lung tissues, amniotic fluid protein profiles, and lung explant and amniotic fluid cocultures in comparison with control and untreated preeclamptic pregnancies. We first identified that a preeclamptic intrauterine environment had a significant adverse impact on fetal lung development, including alterations in fetal lung developmental gene profiles in addition to postnatal alveolar and bronchial changes. Amniotic fluid proteomic analysis and fetal lung explant and amniotic fluid cocultures further demonstrated that maternally administered MEx altered the expression of multiple inflammatory mediators in the preeclamptic intrauterine compartment, resulting in the normalization of fetal lung branching morphogenesis and developmental gene expression. Our evaluation of fetal and postnatal parameters overall suggests that antenatal MEx treatment may provide a highly valuable preventative therapeutic modality for amelioration of lung development in preeclamptic disease.<\/jats:p>","DOI":"10.1165\/rcmb.2021-0307oc","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T17:52:18Z","timestamp":1633542738000},"page":"86-95","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":40,"title":["Antenatal Mesenchymal Stromal Cell Extracellular Vesicle Therapy Prevents Preeclamptic Lung Injury in Mice"],"prefix":"10.1093","volume":"66","author":[{"given":"Elizabeth S.","family":"Taglauer","sequence":"first","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles","family":"Fernandez-Gonzalez","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth R.","family":"Willis","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Reis","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Yeung","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence S.","family":"Prince","sequence":"additional","affiliation":[{"name":"Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and"},{"name":"Lucile Packard Children\u2019s Hospital, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8315-7828","authenticated-orcid":false,"given":"S. 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