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Although the pathogenesis of pulmonary hypoplasia is not fully elucidated, there is now evidence that CDH patients have missing or dysregulated microRNAs (miRNAs) that regulate lung development. A prenatal therapy that supplements these missing\/dysregulated miRNAs could be a strategy to rescue normal lung development. Extracellular vesicles (EVs), also known as exosomes when of small dimensions, are lipid\u2010bound nanoparticles that can transfer their heterogeneous cargo (proteins, lipids, small RNAs) to target cells to induce biological responses. Herein, we review all studies that show evidence for stem cell\u2010derived EVs as a regenerative therapy to rescue normal development in CDH fetal lungs. Particularly, we report studies showing that administration of EVs derived from amniotic fluid stem cells (AFSC\u2010EVs) to models of pulmonary hypoplasia promotes fetal lung growth and maturation via transfer of miRNAs that are known to regulate lung developmental processes. We also describe that stem cell\u2010derived EVs exert effects on vascular remodeling, thus possibly preventing postnatal pulmonary hypertension. Finally, we discuss future perspectives and challenges to translate this promising stem cell EV\u2010based therapy to clinical practice.<\/jats:p>","DOI":"10.1002\/pd.6117","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T07:43:25Z","timestamp":1645515805000},"page":"364-372","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Fetal lung regeneration using stem cell\u2010derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7102-1322","authenticated-orcid":false,"given":"Rebeca Lopes","family":"Figueira","sequence":"first","affiliation":[{"name":"Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Division of General and Thoracic Surgery The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8307-3306","authenticated-orcid":false,"given":"Lina","family":"Antounians","sequence":"additional","affiliation":[{"name":"Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Division of General and Thoracic Surgery The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1391-8921","authenticated-orcid":false,"given":"Elke","family":"Zani\u2010Ruttenstock","sequence":"additional","affiliation":[{"name":"Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Division of General and Thoracic Surgery The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5947-6500","authenticated-orcid":false,"given":"Kasra","family":"Khalaj","sequence":"additional","affiliation":[{"name":"Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Division of General and Thoracic Surgery The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2283-9846","authenticated-orcid":false,"given":"Augusto","family":"Zani","sequence":"additional","affiliation":[{"name":"Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Division of General and Thoracic Surgery The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Surgery University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2020.06.022"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.07.006"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.31.4.450"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2014.09.007"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2021.108769"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-020-01191-x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2017.00195"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199405000-00002"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199610000-00002"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2005.12.007"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.20550.1"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0219732"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.5323"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.19186"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2018.12.010"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026983"},{"key":"e_1_2_13_18_1","first-page":"2112","article-title":"Fetal surgery for severe left diaphragmatic hernia. 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