Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study.
Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. St...
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oai:doaj.org-article:5beccccd0a164ad4b27262e14043fec02021-11-18T09:01:45ZAnti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study.1932-620310.1371/journal.pone.0069299https://doaj.org/article/5beccccd0a164ad4b27262e14043fec02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936322/?tool=EBIhttps://doaj.org/toc/1932-6203Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.Yuben MoodleyVijesh VaghjianiJames ChanSvetlana BalticMarisa RyanJorge TchongueChrishan S SamuelPadma MurthiOrnella ParoliniUrsula ManuelpillaiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e69299 (2013) |
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Medicine R Science Q Yuben Moodley Vijesh Vaghjiani James Chan Svetlana Baltic Marisa Ryan Jorge Tchongue Chrishan S Samuel Padma Murthi Ornella Parolini Ursula Manuelpillai Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study. |
description |
Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury. |
format |
article |
author |
Yuben Moodley Vijesh Vaghjiani James Chan Svetlana Baltic Marisa Ryan Jorge Tchongue Chrishan S Samuel Padma Murthi Ornella Parolini Ursula Manuelpillai |
author_facet |
Yuben Moodley Vijesh Vaghjiani James Chan Svetlana Baltic Marisa Ryan Jorge Tchongue Chrishan S Samuel Padma Murthi Ornella Parolini Ursula Manuelpillai |
author_sort |
Yuben Moodley |
title |
Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study. |
title_short |
Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study. |
title_full |
Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study. |
title_fullStr |
Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study. |
title_full_unstemmed |
Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study. |
title_sort |
anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/5beccccd0a164ad4b27262e14043fec0 |
work_keys_str_mv |
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