Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

Phuong-Uyen C. Dinh, Dipti Paudel, Hayden Brochu, Kristen D. Popowski, M. Cyndell Gracieux, Jhon Cores, Ke Huang, M. Taylor Hensley, Erin Harrell, Adam C. Vandergriff, Arianna K. George, Raina T. Barrio, Shiqi Hu, Tyler A. Allen, Kevin Blackburn, Thomas G. Caranasos, Xinxia Peng, Lauren V. Schnabel, Kenneth B. Adler, Leonard J. Lobo, Michael B. Goshe and Ke Cheng ()
Additional contact information
Phuong-Uyen C. Dinh: North Carolina State University
Dipti Paudel: North Carolina State University
Hayden Brochu: North Carolina State University
Kristen D. Popowski: North Carolina State University
M. Cyndell Gracieux: North Carolina State University
Jhon Cores: North Carolina State University
Ke Huang: North Carolina State University
M. Taylor Hensley: North Carolina State University
Erin Harrell: North Carolina State University
Adam C. Vandergriff: University of North Carolina at Chapel Hill and North Carolina State University
Arianna K. George: North Carolina State University
Raina T. Barrio: North Carolina State University
Shiqi Hu: North Carolina State University
Tyler A. Allen: North Carolina State University
Kevin Blackburn: North Carolina State University
Thomas G. Caranasos: Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill
Xinxia Peng: North Carolina State University
Lauren V. Schnabel: North Carolina State University
Kenneth B. Adler: North Carolina State University
Leonard J. Lobo: University of North Carolina at Chapel Hill
Michael B. Goshe: North Carolina State University
Ke Cheng: North Carolina State University

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.

Date: 2020
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DOI: 10.1038/s41467-020-14344-7

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