Deakin University
Browse

File(s) under permanent embargo

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

Version 2 2024-06-02, 23:04
Version 1 2023-07-14, 04:30
journal contribution
posted on 2023-07-14, 04:30 authored by MCW Chan, DIT Kuok, CYH Leung, KPY Hui, SA Valkenburg, EHY Lau, JM Nicholls, X Fang, Y Guan, JW Lee, RWY Chan, RG Webster, MA Matthay, JSM Peiris
Influenza 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.

History

Journal

Proceedings of the National Academy of Sciences of the United States of America

Volume

113

Pagination

3621-3626

Location

United States

ISSN

0027-8424

eISSN

1091-6490

Language

en

Publication classification

C1.1 Refereed article in a scholarly journal

Issue

13

Publisher

Proceedings of the National Academy of Sciences