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

被引:345
作者
Dinh, Phuong-Uyen C. [1 ,2 ]
Paudel, Dipti [3 ]
Brochu, Hayden [1 ]
Popowski, Kristen D. [1 ,2 ]
Gracieux, M. Cyndell [3 ]
Cores, Jhon [2 ,4 ]
Huang, Ke [1 ,2 ]
Hensley, M. Taylor [1 ]
Harrell, Erin [1 ]
Vandergriff, Adam C. [4 ]
George, Arianna K. [3 ]
Barrio, Raina T. [5 ]
Hu, Shiqi [1 ,4 ]
Allen, Tyler A. [1 ,2 ]
Blackburn, Kevin [3 ]
Caranasos, Thomas G. [6 ]
Peng, Xinxia [1 ,2 ,7 ]
Schnabel, Lauren V. [2 ,8 ]
Adler, Kenneth B. [1 ]
Lobo, Leonard J. [9 ]
Goshe, Michael B. [3 ]
Cheng, Ke [1 ,2 ,4 ]
机构
[1] North Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC 27695 USA
[2] North Carolina State Univ, Comparat Med Inst, Raleigh, NC 27695 USA
[3] North Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA
[4] Univ North Carolina Chapel Hill & North Carolina, Joint Dept Biomed Engn, Raleigh, NC 27695 USA
[5] North Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA
[6] Univ North Carolina Chapel Hill, Div Cardiothorac Surg, Chapel Hill, NC 27599 USA
[7] North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA
[8] North Carolina State Univ, Dept Clin Sci, Raleigh, NC 27695 USA
[9] Univ North Carolina Chapel Hill, Div Pulm Dis & Crit Care Med, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
MESENCHYMAL STEM-CELLS; MATRIX METALLOPROTEINASES; MYOCARDIAL-INFARCTION; MESSENGER-RNA; ANIMAL-MODELS; EXPRESSION; MICROVESICLES; ANGIOGENESIS; THERAPIES; SAFETY;
D O I
10.1038/s41467-020-14344-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung spheroid cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung spheroid cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem cells.
引用
收藏
页数:14
相关论文
共 59 条
[1]   EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 MESSENGER-RNA IN HUMAN IDIOPATHIC PULMONARY FIBROSIS [J].
ANTONIADES, HN ;
NEVILLEGOLDEN, J ;
GALANOPOULOS, T ;
KRADIN, RL ;
VALENTE, AJ ;
GRAVES, DT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5371-5375
[2]   Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models [J].
Bai, Lianhua ;
Lennon, Donald P. ;
Caplan, Arnold I. ;
DeChant, Anne ;
Hecker, Jordan ;
Kranso, Janet ;
Zaremba, Anita ;
Miller, Robert H. .
NATURE NEUROSCIENCE, 2012, 15 (06) :862-U86
[3]   Stem cell paracrine actions and tissue regeneration [J].
Baraniak, Priya R. ;
McDevitt, Todd C. .
REGENERATIVE MEDICINE, 2010, 5 (01) :121-143
[4]   ELEVATED IL-8 AND MCP-1 IN THE BRONCHOALVEOLAR LAVAGE FLUID OF PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS AND PULMONARY SARCOIDOSIS [J].
CAR, BD ;
MELONI, F ;
LUISETTI, M ;
SEMENZATO, G ;
GIALDRONIGRASSI, G ;
WALZ, A .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1994, 149 (03) :655-659
[5]   Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis [J].
Cores, Jhon ;
Hensley, M. Taylor ;
Kinlaw, Kathryn ;
Rikard, S. Michaela ;
Phuong-Uyen Dinh ;
Paudel, Dipti ;
Tang, Junnan ;
Vandergriff, Adam C. ;
Allen, Tyler A. ;
Li, Yazhou ;
Liu, Jianhua ;
Niu, Bo ;
Chi, Yuepeng ;
Caranasos, Thomas ;
Lobo, Leonard J. ;
Cheng, Ke .
STEM CELLS TRANSLATIONAL MEDICINE, 2017, 6 (10) :1905-1916
[6]   Progress Toward Improving Animal Models for Idiopathic Pulmonary Fibrosis [J].
Degryse, Amber L. ;
Lawson, William E. .
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 2011, 341 (06) :444-449
[7]   Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies [J].
Dinh, Phuong-Uyen C. ;
Cores, Jhon ;
Hensley, M. Taylor ;
Vandergriff, Adam C. ;
Tang, Junnan ;
Allen, Tyler A. ;
Caranasos, Thomas G. ;
Adler, Kenneth B. ;
Lobo, Leonard J. ;
Cheng, Ke .
RESPIRATORY RESEARCH, 2017, 18
[8]   miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades [J].
Friedlaender, Marc R. ;
Mackowiak, Sebastian D. ;
Li, Na ;
Chen, Wei ;
Rajewsky, Nikolaus .
NUCLEIC ACIDS RESEARCH, 2012, 40 (01) :37-52
[9]   Diverse functions of matrix metalloproteinases during fibrosis [J].
Giannandrea, Matthew ;
Parks, William C. .
DISEASE MODELS & MECHANISMS, 2014, 7 (02) :193-203
[10]   Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) A Phase I Safety Clinical Trial [J].
Glassberg, Marilyn K. ;
Minkiewicz, Julia ;
Toonkel, Rebecca L. ;
Simonet, Emmanuelle S. ;
Rubio, Gustavo A. ;
DiFede, Darcy ;
Shafazand, Shirin ;
Khan, Aisha ;
Pujol, Marietsy V. ;
LaRussa, Vincent F. ;
Lancaster, Lisa H. ;
Rosen, Glenn D. ;
Fishman, Joel ;
Mageto, Yolanda N. ;
Mendizabal, Adam ;
Hare, Joshua M. .
CHEST, 2017, 151 (05) :971-981