{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T16:43:49Z","timestamp":1783097029107,"version":"3.54.6"},"reference-count":38,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["R01 HL083019"],"award-info":[{"award-number":["R01 HL083019"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["K01 HL084683-05"],"award-info":[{"award-number":["K01 HL084683-05"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000965","name":"American Federation for Aging Research (AFAR)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:p> Although different preclinical models have demonstrated a favorable role for bone marrow-derived mesenchymal stem cells (B-MSC) in preventing fibrosis, this protective effect is not observed with late administration of these cells, when fibrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (antifibrotic) or miR-154 (profibrotic) could alter lung fibrosis in a murine bleomycin model. Using lentiviral vectors, we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associated with changes in the mesenchymal properties of B-MSCs and in their cytokine expression. Modified B-MSCs were intravenously administered to mice at day 7 after bleomycin instillation, and the mice were euthanized at day 14. Bleomycin-injured animals that were treated with let-7d cells were found to recover quicker from the initial weight loss compared with the other treatment groups. Interestingly, animals treated with miR-154 cells had the lowest survival rate. Although a slight reduction in collagen mRNA levels was observed in lung tissue from let-7d mice, no significant differences were observed in Ashcroft score and OH-proline. However, the distinctive expression in cytokines and CD45-positive cells in the lung suggests that the differential effects observed in both miRNA mice groups were related to an effect on the immunomodulation function. Our results establish the use of miRNA-modified mesenchymal stem cells as a potential future research in lung fibrosis. <\/jats:p>","DOI":"10.1152\/ajplung.00323.2016","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T22:27:36Z","timestamp":1491517656000},"page":"L92-L103","source":"Crossref","is-referenced-by-count":35,"title":["Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model"],"prefix":"10.1152","volume":"313","author":[{"given":"Luai","family":"Huleihel","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"},{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"},{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel;"},{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Yale University, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobo","family":"Sellares","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"},{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"},{"name":"Servei de Pneumologia, Hospital Cl\u00ednic, August Pi i Sunyer Biomedical Research Institute, Universitat de Barcelona, Barcelona, Spain;"},{"name":"Centro de Investigaci\u00f3n Biomedica En Red-Enfermedades Respiratorias, Institut Investigacions Biom\u00e8diques, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayra","family":"Cardenes","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"},{"name":"The Dorothy P. and Richard P. 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