Document Type

Article

Source Publication Title

PLoS ONE

First Page

1

Last Page

10

DOI

10.1371/journal.pone.0171165

Abstract

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.

Publication Date

2-2-2017

Language

English

Comments

We gratefully acknowledge the support from a new faculty start-up fund (YH) at the University of Texas at Arlington, and the National Heart, Lung and Blood Institute grants R01 HL40070 (CCWH) and U01 HL111146 (CCWH and KTN). RP is the recipient of a Mentored Clinical and Translational Research Scholar Award (KL2TR001103) from the National Center for Advancing Translational Science of the National Institutes of Health. We appreciate the technical assistance of Hua Lu. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Department of Bioengineering, The University of Texas at Arlington

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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