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

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. Emphysema: Nanotechnology for lung repair Tiny artificial sacs derived from stem cells show promise for delivering natural growth factor molecules to treat emphysema. Yeon-Mok Oh of the University of Ulsan, with colleagues from elsewhere in South Korea made the sacs, called nanovesicles, from fragments of stem cells derived from fat tissue. The nanovesicles carried a cargo of growth factor molecules known to promote regeneration of healthy cells in diseased lungs. The vesicles were injected into mice with an artificially induced lung condition that serves as a model of emphysema. This led to the same beneficial regeneration of lung tissue as using intact stem cells or the natural secretory vesicles derived from stem cells but lower doses were required. The results suggest that artificial nanovesicles could be developed into a more economic and effective treatment tha