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Article

Concentrated Secretome of Adipose Stromal Cells Limits Influenza A Virus-Induced Lung Injury in Mice

1
Division of Pulmonary, Critical Care and Sleep, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2
Theratome Bio, Inc., Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Lilach O. Lerman
Cells 2021, 10(4), 720; https://doi.org/10.3390/cells10040720
Received: 3 March 2021 / Revised: 19 March 2021 / Accepted: 22 March 2021 / Published: 24 March 2021
Despite vaccination and antivirals, influenza remains a communicable disease of high burden, with limited therapeutic options available to patients that develop complications. Here, we report the development and preclinical characterization of Adipose Stromal Cell (ASC) concentrated secretome (CS), generated by process adaptable to current Good Manufacturing Practices (cGMP) standards. We demonstrate that ASC-CS limits pulmonary histopathological changes, infiltration of inflammatory cells, protein leak, water accumulation, and arterial oxygen saturation (spO2) reduction in murine model of lung infection with influenza A virus (IAV) when first administered six days post-infection. The ability to limit lung injury is sustained in ASC-CS preparations stored at −80 °C for three years. Priming of the ASC with inflammatory factors TNFα and IFNγ enhances ASC-CS ability to suppress lung injury. IAV infection is associated with dramatic increases in programmed cell death ligand (PDL1) and angiopoietin 2 (Angpt2) levels. ASC-CS application significantly reduces both PDL1 and Angpt2 levels. Neutralization of PDL1 with anti-mouse PDL1 antibody starting Day6 onward effectively ablates lung PDL1, but only non-significantly reduces Angpt2 release. Most importantly, late-phase PDL1 neutralization results in negligible suppression of protein leakage and inflammatory cell infiltration, suggesting that suppression of PDL1 does not play a critical role in ASC-CS therapeutic effects. View Full-Text
Keywords: adipose stromal cell; secretome; lung injury; influenza; angiopoietin 2; PDL1 adipose stromal cell; secretome; lung injury; influenza; angiopoietin 2; PDL1
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MDPI and ACS Style

Bogatcheva, N.V.; Coleman, M.E. Concentrated Secretome of Adipose Stromal Cells Limits Influenza A Virus-Induced Lung Injury in Mice. Cells 2021, 10, 720. https://doi.org/10.3390/cells10040720

AMA Style

Bogatcheva NV, Coleman ME. Concentrated Secretome of Adipose Stromal Cells Limits Influenza A Virus-Induced Lung Injury in Mice. Cells. 2021; 10(4):720. https://doi.org/10.3390/cells10040720

Chicago/Turabian Style

Bogatcheva, Natalia V., and Michael E. Coleman 2021. "Concentrated Secretome of Adipose Stromal Cells Limits Influenza A Virus-Induced Lung Injury in Mice" Cells 10, no. 4: 720. https://doi.org/10.3390/cells10040720

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