Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig

Mahesh Khatri1, Levi Arthur Richardson2, Tea Meulia3

  • 1Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA. khatri.14@osu.edu.

Abstract

Insights

Mesenchymal stem cell-derived extracellular vesicles (EVs) show potent anti-influenza and anti-inflammatory effects. This preclinical study suggests MSC-EVs could be a novel cell-free therapy for influenza treatment.

Area of Science:

  • Regenerative Medicine
  • Virology
  • Immunology

Background:

  • Mesenchymal stem cells (MSCs) exert therapeutic effects via secreted factors, including extracellular vesicles (EVs).
  • MSC-EVs replicate MSC benefits in preclinical models, offering potential as cell-free therapies.
  • Influenza viruses pose a significant global health threat due to constant evolution and drug resistance, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the efficacy of MSC-EV treatment in mitigating influenza virus-induced acute lung injury.
  • To evaluate the anti-viral and immunomodulatory properties of MSC-EVs in a preclinical influenza model.

Main Methods:

  • Extracellular vesicles (EVs) were isolated from swine bone marrow-derived MSCs.
  • MSC-EVs characterized via electron microscopy and flow cytometry for mesenchymal markers.
  • In vitro anti-influenza activity assessed in lung epithelial cells; in vivo efficacy evaluated in a pig influenza model.

Main Results:

  • MSC-EVs inhibited hemagglutination and replication of diverse influenza strains in vitro.
  • EVs were incorporated into lung epithelial cells, delivering RNA to confer anti-viral effects.
  • In pigs, MSC-EVs reduced viral shedding, lung replication, pro-inflammatory cytokine production, and lung lesions.

Conclusions:

  • MSC-derived extracellular vesicles demonstrate significant anti-influenza and anti-inflammatory capabilities.
  • These findings support the potential of MSC-EVs as a cell-free therapeutic approach for influenza infections in humans.

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