title: Serelaxin improves the therapeutic efficacy of RXFP1-expressing human amnion epithelial cells in experimental allergic airway disease.
abstract: 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 1×106cells 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.
authors.affiliation: Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia chrishan.samuel@monash.edu simon.royce@monash.edu.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Royce
authors.affiliation: Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Tominaga
authors.affiliation: Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Shen
authors.affiliation: Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Krupesh P
authors.initials: KP
authors.lastname: Patel
authors.affiliation: 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.
authors.forename: Brooke M
authors.initials: BM
authors.lastname: Huuskes
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
authors.affiliation: 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.
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Ricardo
authors.affiliation: Fibrosis Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia chrishan.samuel@monash.edu simon.royce@monash.edu.
authors.forename: Chrishan S
authors.initials: CS
authors.lastname: Samuel
mesh_terms: D000650:Amnion / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics* / Q000378:metabolism; D012065:Relaxin / Q000008:administration & dosage*
chemical_list: C095068:RLN2 protein, human; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin
keywords: airway remodelling; asthma; fibrosis; serelaxin; stem cells