Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration

用于高通量研究肺部疾病和再生的脱细胞人肺和猪肺三维支架

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作者:Darcy E Wagner,Nicholas R Bonenfant,Dino Sokocevic,Michael J DeSarno,Zachary D Borg,Charles S Parsons,Elice M Brooks,Joseph J Platz,Zain I Khalpey,David M Hoganson,Bin Deng,Ying W Lam,Rachael A Oldinski,Takamaru Ashikaga,Daniel J Weiss

Abstract

Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de and recellularization of large animal and human lungs including techniques which allow multiple small segments (∼ 1-3 cm(3)) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold.

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