title: Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration.
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.
authors.affiliation: University of Vermont, Department of Medicine, 226 Health Sciences, Research Facility Center, Burlington, VT 05405, USA. Electronic address: Darcy.wagner@med.uvm.edu.
authors.forename: Darcy E
authors.initials: DE
authors.lastname: Wagner
authors.affiliation: University of Vermont, Department of Medicine, 226 Health Sciences, Research Facility Center, Burlington, VT 05405, USA. Electronic address: Nicholas.Bonenfant@med.uvm.edu.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Bonenfant
authors.affiliation: University of Vermont, Department of Medicine, 226 Health Sciences, Research Facility Center, Burlington, VT 05405, USA. Electronic address: Dino.Sokocevic@med.uvm.edu.
authors.forename: Dino
authors.initials: D
authors.lastname: Sokocevic
authors.affiliation: University of Vermont, Department of Medical Biostatistics, 27 Hills Building, Burlington, VT 05405, USA. Electronic address: mdesarno@uvm.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: DeSarno
authors.affiliation: University of Vermont, Department of Medicine, 226 Health Sciences, Research Facility Center, Burlington, VT 05405, USA. Electronic address: zachary.borg@med.uvm.edu.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Borg
authors.affiliation: University of Vermont, Department of Surgery, Fletcher House 301, Burlington, VT 05405, USA. Electronic address: charles.parsons@vtmednet.org.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Parsons
authors.affiliation: University of Vermont, Department of Medicine, 226 Health Sciences, Research Facility Center, Burlington, VT 05405, USA. Electronic address: elice.brooks@med.uvm.edu.
authors.forename: Elice M
authors.initials: EM
authors.lastname: Brooks
authors.affiliation: University of Vermont, Department of Surgery, Fletcher House 301, Burlington, VT 05405, USA. Electronic address: Joseph.Platz@med.uvm.edu.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Platz
authors.affiliation: University of Arizona, Department of Surgery, 1501 North Campbell Avenue, Tucson, AZ 85724, USA. Electronic address: zkhalpey@surgery.arizona.edu.
authors.forename: Zain I
authors.initials: ZI
authors.lastname: Khalpey
authors.affiliation: Washington University in St. Louis, Department of Surgery, 1 Barnes Jewish Plaza, 3108 Queeny Tower, St. Louis, MO 63110, USA. Electronic address: hogansondm@wudosis.wustl.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Hoganson
authors.affiliation: University of Vermont, Department of Biology, 311 Marsh Life Sciences, Burlington, VT 05405, USA. Electronic address: bdeng@uvm.edu.
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.affiliation: University of Vermont, Department of Biology, 311 Marsh Life Sciences, Burlington, VT 05405, USA. Electronic address: Ying-Wai.Lam@uvm.edu.
authors.forename: Ying W
authors.initials: YW
authors.lastname: Lam
authors.affiliation: University of Vermont, College of Engineering and Mathematics, 301 Votey Hall, 33 Colchester Ave, Burlington, VT 05405, USA. Electronic address: oldinski@uvm.edu.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Oldinski
authors.affiliation: University of Vermont, Department of Medical Biostatistics, 27 Hills Building, Burlington, VT 05405, USA. Electronic address: Takamaru.Ashikaga@uvm.edu.
authors.forename: Takamaru
authors.initials: T
authors.lastname: Ashikaga
authors.affiliation: University of Vermont, Department of Medicine, 226 Health Sciences, Research Facility Center, Burlington, VT 05405, USA. Electronic address: dweiss@uvm.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002102:Cadaver; D042783:Endothelial Cells / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007259:Infrared Rays; D008168:Lung / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D008171:Lung Diseases / Q000473:pathology / Q000503:physiopathology*; D013058:Mass Spectrometry; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010477:Perfusion; D012038:Regeneration; D034421:Sus scrofa; D013817:Thermography; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
keywords: Acellular matrix; Endothelial cell; Epithelial cell; Extracellular matrix (ECM); Human lung fibroblast; Mesenchymal stem cell