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Article: Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

TitleHuman mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo
Authors
Issue Date2016
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2016, v. 113 n. 13, p. 3621-3626 How to Cite?
AbstractInfluenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.
Persistent Identifierhttp://hdl.handle.net/10722/224843
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorChan, MCW-
dc.contributor.authorKuok, DIT-
dc.contributor.authorLeung, CYH-
dc.contributor.authorHui, KPY-
dc.contributor.authorDoak, SA-
dc.contributor.authorLau, EHY-
dc.contributor.authorNicholls, JM-
dc.contributor.authorFang, X-
dc.contributor.authorGuan, Y-
dc.contributor.authorLee, JW-
dc.contributor.authorChan, WY-
dc.contributor.authorWebster, RG-
dc.contributor.authorMatthay, MA-
dc.contributor.authorPeiris, JSM-
dc.date.accessioned2016-04-18T03:33:24Z-
dc.date.available2016-04-18T03:33:24Z-
dc.date.issued2016-
dc.identifier.citationProceedings of the National Academy of Sciences, 2016, v. 113 n. 13, p. 3621-3626-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/224843-
dc.description.abstractInfluenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.titleHuman mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo-
dc.typeArticle-
dc.identifier.emailChan, MCW: mchan@hku.hk-
dc.identifier.emailLeung, CYH: cyhleung@hku.hk-
dc.identifier.emailHui, KPY: kenrie@hku.hk-
dc.identifier.emailDoak, SA: sophiev@hku.hk-
dc.identifier.emailLau, EHY: ehylau@hku.hk-
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hk-
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hk-
dc.identifier.emailChan, WY: reneewy@hku.hk-
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hk-
dc.identifier.authorityChan, MCW=rp00420-
dc.identifier.authorityLeung, CYH=rp00307-
dc.identifier.authorityDoak, SA=rp02141-
dc.identifier.authorityLau, EHY=rp01349-
dc.identifier.authorityNicholls, JM=rp00364-
dc.identifier.authorityGuan, Y=rp00397-
dc.identifier.authorityChan, WY=rp01596-
dc.identifier.authorityPeiris, JSM=rp00410-
dc.identifier.doi10.1073/pnas.1601911113-
dc.identifier.pmid26976597-
dc.identifier.pmcidPMC4822574-
dc.identifier.hkuros257599-
dc.identifier.volume113-
dc.identifier.issue13-
dc.identifier.spage3621-
dc.identifier.epage3626-
dc.publisher.placeUnited States-

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