Current asthma therapies primarily target airway inflammation (AI) and suppress episodes of airway hyperresponsiveness (AHR) but fail to treat airway remodelling (AWR), which can develop independently of AI and contribute to irreversible airway obstruction. The present study compared the anti-remodelling and therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) to that of human amnion epithelial stem cells (AECs) in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic (serelaxin; RLX). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD, were either vehicle-treated (OVA alone) or treated with MSCs or AECs alone [intranasally (i.n.)-administered with 1×106 cells once weekly], RLX alone (i.n.-administered with 0.8 mg/ml daily) or a combination of MSCs or AECs and RLX from weeks 9–11 (n=6/group). Measures of AI, AWR and AHR were then assessed. OVA alone exacerbated AI, epithelial damage/thickness, sub-epithelial extracellular matrix (ECM) and total collagen deposition, markers of collagen turnover and AHR compared with that in saline-treated counterparts (all P<0.01 compared with saline-treated controls). RLX or AECs (but not MSCs) alone normalized epithelial thickness and partially diminished the OVA-induced fibrosis and AHR by ∼40–50% (all P<0.05 compared with OVA alone). Furthermore, the combination treatments normalized epithelial thickness, measures of fibrosis and AHR to that in normal mice, and significantly decreased AI. Although AECs alone demonstrated greater protection against the AAD-induced AI, AWR and AHR, compared with that of MSCs alone, combining RLX with MSCs or AECs reversed airway fibrosis and AHR to an even greater extent.
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IL-13 induced actin cytoskeleton rearrangement in human podocytes. Magnification, x60, scale bar, 20μm. For more information please see pp. 2317-2327. Image provided by Chan Chang Yien.
Research Article|
October 20 2016
Serelaxin improves the therapeutic efficacy of RXFP1-expressing human amnion epithelial cells in experimental allergic airway disease
Simon G. Royce;
Simon G. Royce
1
*Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
Correspondence: Associate Professor Chrishan S. Samuel (email [email protected]) or Dr Simon G. Royce ([email protected]).
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Anna M. Tominaga;
Anna M. Tominaga
1
*Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Matthew Shen;
Matthew Shen
*Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Krupesh P. Patel;
Krupesh P. Patel
*Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Brooke M. Huuskes;
Brooke M. Huuskes
†Kidney Regeneration and Stem Cell Laboratory, Development & Stem Cells Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Rebecca Lim;
Rebecca Lim
‡The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria 3800, Australia
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Sharon D. Ricardo;
Sharon D. Ricardo
†Kidney Regeneration and Stem Cell Laboratory, Development & Stem Cells Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Chrishan S. Samuel
*Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
Correspondence: Associate Professor Chrishan S. Samuel (email [email protected]) or Dr Simon G. Royce ([email protected]).
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Publisher: Portland Press Ltd
Received:
May 09 2016
Revision Received:
August 24 2016
Accepted:
September 12 2016
Accepted Manuscript online:
September 19 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (23): 2151–2165.
Article history
Received:
May 09 2016
Revision Received:
August 24 2016
Accepted:
September 12 2016
Accepted Manuscript online:
September 19 2016
Citation
Simon G. Royce, Anna M. Tominaga, Matthew Shen, Krupesh P. Patel, Brooke M. Huuskes, Rebecca Lim, Sharon D. Ricardo, Chrishan S. Samuel; Serelaxin improves the therapeutic efficacy of RXFP1-expressing human amnion epithelial cells in experimental allergic airway disease. Clin Sci (Lond) 1 December 2016; 130 (23): 2151–2165. doi: https://doi.org/10.1042/CS20160328
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