4.8 Article

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

Journal

BIOMATERIALS
Volume 35, Issue 9, Pages 2664-2679

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.11.078

Keywords

Acellular matrix; Endothelial cell; Epithelial cell; Extracellular matrix (ECM); Human lung fibroblast; Mesenchymal stem cell

Funding

  1. NIH ARRA [RC4HL106625]
  2. NHLBI [R21HL094611, R21HL108689]
  3. UVM Lung Biology Training grant from the NHLBI [T32 HL076122]
  4. Vermont Genetics Network through NIH grant from the INBRE program of the National Institute of General Medical Sciences (NIGMS) [8P20GM103449]
  5. National Center for Research Resources (NCRR)

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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 (similar to 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. (C) 2013 Elsevier Ltd. All rights reserved.

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