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

无细胞人类和猪肺的三维支架可用于肺部疾病和再生的高通量研究

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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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