Exp Mol Med.  2017 Jan;49(1):e284. 10.1038/emm.2016.127.

Adipose stem cell-derived nanovesicles inhibit emphysema primarily via an FGF2-dependent pathway

Affiliations
  • 1Asan Institute for Life Sciences, Seoul, Korea.
  • 2Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Seoul, Korea. ymoh55@amc.seoul.kr
  • 3Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea.
  • 4Department of Pulmonary and Critical Care Medicine, Asan Medical Center, Seoul, Korea.

Abstract

Cell therapy using stem cells has produced therapeutic benefits in animal models of COPD. Secretory mediators are proposed as one mechanism for stem cell effects because very few stem cells engraft after injection into recipient animals. Recently, nanovesicles that overcome the disadvantages of natural exosomes have been generated artificially from cells. We generated artificial nanovesicles from adipose-derived stem cells (ASCs) using sequential penetration through polycarbonate membranes. ASC-derived artificial nanovesicles displayed a 100"‰nm-sized spherical shape similar to ASC-derived natural exosomes and expressed both exosomal and stem cell markers. The proliferation rate of lung epithelial cells was increased in cells treated with ASC-derived artificial nanovesicles compared with cells treated with ASC-derived natural exosomes. The lower dose of ASC-derived artificial nanovesicles had similar regenerative capacity compared with a higher dose of ASCs and ASC-derived natural exosomes. In addition, FGF2 levels in the lungs of mice treated with ASC-derived artificial nanovesicles were increased. The uptake of ASC-derived artificial nanovesicles was inhibited by heparin, which is a competitive inhibitor of heparan sulfate proteoglycan that is associated with FGF2 signaling. Taken together, the data indicate that lower doses of ASC-derived artificial nanovesicles may have beneficial effects similar to higher doses of ASCs or ASC-derived natural exosomes in an animal model with emphysema, suggesting that artificial nanovesicles may have economic advantages that warrant future clinical studies.


MeSH Terms

Animals
Cell- and Tissue-Based Therapy
Emphysema*
Epithelial Cells
Exosomes
Fibroblast Growth Factor 2
Heparan Sulfate Proteoglycans
Heparin
Lung
Membranes
Mice
Models, Animal
Pulmonary Disease, Chronic Obstructive
Stem Cells
Fibroblast Growth Factor 2
Heparan Sulfate Proteoglycans
Heparin
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