{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:42:56Z","timestamp":1787229776302,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center","award":["2017\/01\/X\/NZ3\/00250"],"award-info":[{"award-number":["2017\/01\/X\/NZ3\/00250"]}]},{"name":"National Science Center","award":["UMO-2014\/14\/M\/NZ3\/00475"],"award-info":[{"award-number":["UMO-2014\/14\/M\/NZ3\/00475"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1HL073742"],"award-info":[{"award-number":["RO1HL073742"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Alveolar type 2 (AT2) cells and bronchioalveolar stem cells (BASC) perform critical regenerative functions in response to lung damage. Published data show that nonhematopoietic, bone marrow-derived \u201cvery small embryonic-like stem cells\u201d (VSELs) can differentiate in vivo into surfactant protein C (SPC)-producing AT2 cells in the lung. Here, we test directly whether VSEL-derived BASC and AT2 cells function to produce differentiated progeny. Methods: using a reporter mouse in which the H2B-GFP fusion protein is driven from the murine SPC promoter, we tested whether bone marrow-derived VSELs or non-VSEL\/nonhematopoietic stem cells (non-VSEL\/non-HSCs) can differentiate into AT2 and BASC cells that function as progenitor cells. Immediately following bleomycin administration, WT recipient mice underwent intravenous administration of VSELs or non-VSEL\/non-HSCs from SPC H2B-GFP mice. GFP+ AT2 and BASC were isolated and tested for progenitor activity using in vitro organoid assays. Results: after 21 days in vivo, we observed differentiation of VSELs but not non-VSEL\/non-HSCs into phenotypic AT2 and BASC consistent with previous data in irradiated recipients. Subsequent in vitro organoid assays revealed that VSEL-derived AT2 and BASC maintained physiological potential for differentiation and self-renewal. Conclusion: these findings prove that VSELs produce functional BASC and AT2 cells, and this may open new avenues using VSELs to develop effective cell therapy approaches for patients with lung injury.<\/jats:p>","DOI":"10.3390\/cells10071570","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:02:10Z","timestamp":1624366930000},"page":"1570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Bone Marrow-Derived VSELs Engraft as Lung Epithelial Progenitor Cells after Bleomycin-Induced Lung Injury"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0052-136X","authenticated-orcid":false,"given":"Andrzej K.","family":"Ciechanowicz","sequence":"first","affiliation":[{"name":"Department of Regenerative Medicine, Center for Preclinical Research and Technology, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4272-2266","authenticated-orcid":false,"given":"Katarzyna","family":"Sielatycka","sequence":"additional","affiliation":[{"name":"Institute of Biology, Faculty of Exact and Natural Sciences, University of Szczecin, 71-415 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Cymer","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Center for Preclinical Research and Technology, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Skoda","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Center for Preclinical Research and Technology, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malwina","family":"Suszy\u0144ska","sequence":"additional","affiliation":[{"name":"Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2205-1154","authenticated-orcid":false,"given":"Kamila","family":"Bujko","sequence":"additional","affiliation":[{"name":"Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz Z.","family":"Ratajczak","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Center for Preclinical Research and Technology, Medical University of Warsaw, 02-097 Warsaw, Poland"},{"name":"Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane S.","family":"Krause","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine, Cell Biology and Pathology and the Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Kucia","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Center for Preclinical Research and Technology, Medical University of Warsaw, 02-097 Warsaw, Poland"},{"name":"Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1177\/1534735414534463","article-title":"Intravenous Vitamin C and Cancer: A Systematic Review","volume":"13","author":"Fritz","year":"2014","journal-title":"Integr. 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