title: Mesenchymal stromal (stem) cell therapy fails to improve outcomes in experimental severe influenza.
abstract: BACKGROUND
  Severe influenza remains a major public health threat and is responsible for thousands of deaths annually. Increasing antiviral resistance and limited effectiveness of current therapies highlight the need for new approaches to influenza treatment. Extensive pre-clinical data have shown that mesenchymal stromal (stem) cell (MSC) therapy can induce anti-inflammatory effects and enhance repair of the injured lung. We hypothesized that MSC therapy would improve survival, dampen lung inflammation and decrease acute lung injury (ALI) in a murine model of severe influenza.
  
  
  METHODS
  C57Bl/6 mice were infected with influenza A/PuertoRico/8/34 (mouse-adapted H1N1) or influenza A/Mexico/4108/2009 (swine-origin pandemic H1N1) and administered human or mouse MSCs via the tail vein, either pre- or post- infection. MSC efficacy was evaluated as both an independent and adjunctive treatment strategy in combination with the antiviral agent, oseltamivir. Weight loss and survival were monitored. Inflammatory cells, cytokine/chemokines (IFN-γ, CXCL10, CCL2 and CCL5) and markers of ALI (total protein and IgM), were measured in bronchoalveolar lavage fluid and lung parenchyma.
  
  
  RESULTS
  Administration of murine MSCs or human MSCs in a prophylactic or therapeutic regimen failed to improve survival, decrease pulmonary inflammation/inflammatory cell counts or prevent ALI in influenza virus-infected mice. MSCs administered in combination with oseltamivir also failed to improve outcomes.
  
  
  CONCLUSIONS
  Despite similarities in the clinical presentation and pathobiology of ALI and severe influenza, our findings suggest that MSC therapy may not be effective for prevention and/or treatment of acute severe influenza.
authors: Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors: Ilyse
authors: I
authors: Darwish
authors: David
authors: D
authors: Banner
authors: Samira
authors: S
authors: Mubareka
authors: Hani
authors: H
authors: Kim
authors: Rickvinder
authors: R
authors: Besla
authors: David J
authors: DJ
authors: Kelvin
authors: Kevin C
authors: KC
authors: Kain
authors: W Conrad
authors: WC
authors: Liles
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000628:therapy* / Q000821:virology; D011014:Pneumonia / Q000473:pathology / Q000821:virology; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents
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