Lung protection by inhalation of exogenous solubilized extracellular matrix
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Date
2017-02-02Author
Wu, Jinglei
Ravikumar, Priya
Nguyen, Kytai Truong
Hsia, Connie C. W.
Hong, Yi
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Decellularized extracellular matrix (ECM) contains complex tissue-specific components that
work in concert to promote tissue repair and constructive remodeling and has been used
experimentally and clinically to accelerate epithelial wound repair, leading us to hypothesize
that lung-derived ECM could mitigate acute lung injury. To explore the therapeutic potential
of ECM for noninvasive delivery to the lung, we decellularized and solubilized porcine lung
ECM, then characterized the composition, concentration, particle size and stability of the
preparation. The ECM preparation at 3.2 mg/mL with average particle size <3 μm was
tested in vitro on human A549 lung epithelial cells exposed to 95% O2 for 24 hours, and in
vivo by tracheal instillation or nebulization into the lungs of rats exposed intermittently or
continuously to 90% O2 for a cumulative 72 hours. Our results showed that the preparation
was enriched in collagen, reduced in glycosaminoglycans, and contained various bioactive
molecules. Particle size was concentration-dependent. Compared to the respective controls
treated with cell culture medium in vitro or saline in vivo, ECM inhalation normalized cell survival and alveolar morphology, and reduced hyperoxia-induced apoptosis and oxidative
damage. This proof-of-concept study established the methodology, feasibility and therapeutic potential of exogenous solubilized ECM for pulmonary cytoprotection, possibly as an
adjunct or potentiator of conventional therapy.
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