Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model
Abstract Acute lung injury (ALI) is a critical condition with limited treatment options. This study evaluates the therapeutic potential of human fetal lung-derived mesenchymal stem cells (hFL-MSCs) in an experimental model of ALI. Our proof-of-concept findings suggest a paradigm shift in the approac...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-91406-0 |
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| author | Mahtab Golmohammadi Mohammad Hasan Sheikhha Fatemeh Ganji Ali Shirani Mahmood Barati Seyed Mehdi Kalantar Seyed Mohammad Amin Haramshahi Nushin Karkuki Osguei Ali Samadikuchaksaraei |
| author_facet | Mahtab Golmohammadi Mohammad Hasan Sheikhha Fatemeh Ganji Ali Shirani Mahmood Barati Seyed Mehdi Kalantar Seyed Mohammad Amin Haramshahi Nushin Karkuki Osguei Ali Samadikuchaksaraei |
| author_sort | Mahtab Golmohammadi |
| collection | DOAJ |
| description | Abstract Acute lung injury (ALI) is a critical condition with limited treatment options. This study evaluates the therapeutic potential of human fetal lung-derived mesenchymal stem cells (hFL-MSCs) in an experimental model of ALI. Our proof-of-concept findings suggest a paradigm shift in the approach to cell sourcing for lung diseases, proposing that fetal lung cells may be potential targets for stem cell differentiation studies when the derived cells are intended to be used for lung cell therapy. After characterizing hFL-MSCs, 18-week fetal lung cells were intratracheally instilled into rats with bleomycin-induced ALI. All the animals were evaluated on days 3 − 28 post-injury for cell count and the cytokines in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, lung tissue histological staining and expression of an extracellular matrix component, inflammatory and fibrotic genes. The findings confirm mesenchymal stem cell identity of the isolated cells and stability in their cell cycle distribution. Analysis of BALF showed that immune cell response to acute inflammation and adaptive immunity was significantly ameliorated by cell therapy with hFL-MSCs. Same results were confirmed by the levels of IL-6, TNF-α, IL-10 and NO in BALF, the lung wet/dry weight ratio and histopathological analysis of lung tissues after H&E and Masson’s trichrome staining. Effective modulation of key pro-inflammatory (Il6, Tnf, Il1b), pro-fibrotic (Tgfb1) and Col1a1 genes were also confirmed after therapy with hFL-MSCs. Our findings suggest that fetal lung tissue-specific stem cells are viable options for lung cell therapy and could be considered as targets for engineering of regenerative cells for lung diseases. |
| format | Article |
| id | doaj-art-7571adca06194c4c8cc01cc7ff255159 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7571adca06194c4c8cc01cc7ff2551592025-08-20T02:15:11ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-025-91406-0Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal modelMahtab Golmohammadi0Mohammad Hasan Sheikhha1Fatemeh Ganji2Ali Shirani3Mahmood Barati4Seyed Mehdi Kalantar5Seyed Mohammad Amin Haramshahi6Nushin Karkuki Osguei7Ali Samadikuchaksaraei8Department of Medical Genetics, Shahid Sadoughi University of Medical SciencesDepartment of Medical Genetics, Shahid Sadoughi University of Medical SciencesLatner Research Laboratories, Division of Thoracic Surgery, University Health NetworkThe Persian Gulf Biomedical Research Institute, Bushehr University of Medical SciencesCellular and Molecular Research Centre, Iran University of Medical SciencesDepartment of Medical Genetics, Shahid Sadoughi University of Medical SciencesCellular and Molecular Research Centre, Iran University of Medical SciencesEposcience Millennium InstituteDepartment of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical SciencesAbstract Acute lung injury (ALI) is a critical condition with limited treatment options. This study evaluates the therapeutic potential of human fetal lung-derived mesenchymal stem cells (hFL-MSCs) in an experimental model of ALI. Our proof-of-concept findings suggest a paradigm shift in the approach to cell sourcing for lung diseases, proposing that fetal lung cells may be potential targets for stem cell differentiation studies when the derived cells are intended to be used for lung cell therapy. After characterizing hFL-MSCs, 18-week fetal lung cells were intratracheally instilled into rats with bleomycin-induced ALI. All the animals were evaluated on days 3 − 28 post-injury for cell count and the cytokines in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, lung tissue histological staining and expression of an extracellular matrix component, inflammatory and fibrotic genes. The findings confirm mesenchymal stem cell identity of the isolated cells and stability in their cell cycle distribution. Analysis of BALF showed that immune cell response to acute inflammation and adaptive immunity was significantly ameliorated by cell therapy with hFL-MSCs. Same results were confirmed by the levels of IL-6, TNF-α, IL-10 and NO in BALF, the lung wet/dry weight ratio and histopathological analysis of lung tissues after H&E and Masson’s trichrome staining. Effective modulation of key pro-inflammatory (Il6, Tnf, Il1b), pro-fibrotic (Tgfb1) and Col1a1 genes were also confirmed after therapy with hFL-MSCs. Our findings suggest that fetal lung tissue-specific stem cells are viable options for lung cell therapy and could be considered as targets for engineering of regenerative cells for lung diseases.https://doi.org/10.1038/s41598-025-91406-0Mesenchymal stem cellsAcute lung injuryPulmonary fibrosis, fetal tissuesCell therapy |
| spellingShingle | Mahtab Golmohammadi Mohammad Hasan Sheikhha Fatemeh Ganji Ali Shirani Mahmood Barati Seyed Mehdi Kalantar Seyed Mohammad Amin Haramshahi Nushin Karkuki Osguei Ali Samadikuchaksaraei Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model Scientific Reports Mesenchymal stem cells Acute lung injury Pulmonary fibrosis, fetal tissues Cell therapy |
| title | Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model |
| title_full | Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model |
| title_fullStr | Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model |
| title_full_unstemmed | Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model |
| title_short | Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model |
| title_sort | human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model |
| topic | Mesenchymal stem cells Acute lung injury Pulmonary fibrosis, fetal tissues Cell therapy |
| url | https://doi.org/10.1038/s41598-025-91406-0 |
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