Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study

Yuben Moodley, V. Vaghjiani, J. Chan, S. Baltić, M. Ryan, J. Tchongue, C.S. Samuel, P. Murthi, O. Parolini, U. Manuelpillai

Research output: Contribution to journalArticle

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Abstract

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. © 2013 Moodley et al.
Original languageEnglish
Pages (from-to)e69299
JournalPLoS One
Volume8
Issue number8
DOIs
Publication statusPublished - 2013

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Adult Stem Cells
Amnion
Lung Injury
Stem cells
anti-inflammatory activity
Mesenchymal Stromal Cells
amnion
stem cells
Anti-Inflammatory Agents
lungs
Lung Diseases
Pulmonary diseases
Bleomycin
Stem Cells
respiratory tract diseases
Injections
Bone Marrow
Epithelial Cells
Cell- and Tissue-Based Therapy
bone marrow

Cite this

Moodley, Y., Vaghjiani, V., Chan, J., Baltić, S., Ryan, M., Tchongue, J., ... Manuelpillai, U. (2013). Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study. PLoS One, 8(8), e69299. https://doi.org/10.1371/journal.pone.0069299
Moodley, Yuben ; Vaghjiani, V. ; Chan, J. ; Baltić, S. ; Ryan, M. ; Tchongue, J. ; Samuel, C.S. ; Murthi, P. ; Parolini, O. ; Manuelpillai, U. / Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study. In: PLoS One. 2013 ; Vol. 8, No. 8. pp. e69299.
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Moodley, Y, Vaghjiani, V, Chan, J, Baltić, S, Ryan, M, Tchongue, J, Samuel, CS, Murthi, P, Parolini, O & Manuelpillai, U 2013, 'Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study' PLoS One, vol. 8, no. 8, pp. e69299. https://doi.org/10.1371/journal.pone.0069299

Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study. / Moodley, Yuben; Vaghjiani, V.; Chan, J.; Baltić, S.; Ryan, M.; Tchongue, J.; Samuel, C.S.; Murthi, P.; Parolini, O.; Manuelpillai, U.

In: PLoS One, Vol. 8, No. 8, 2013, p. e69299.

Research output: Contribution to journalArticle

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T1 - Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study

AU - Moodley, Yuben

AU - Vaghjiani, V.

AU - Chan, J.

AU - Baltić, S.

AU - Ryan, M.

AU - Tchongue, J.

AU - Samuel, C.S.

AU - Murthi, P.

AU - Parolini, O.

AU - Manuelpillai, U.

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AB - 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. © 2013 Moodley et al.

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DO - 10.1371/journal.pone.0069299

M3 - Article

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