title: Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine.
abstract: Lung engineering is a promising technology, relying on re-seeding of either human or xenographic decellularized matrices with patient-derived pulmonary cells. Little is known about the species-specificity of decellularization in various models of lung regeneration, or if species dependent cell-matrix interactions exist within these systems. Therefore decellularized scaffolds were produced from rat, pig, primate and human lungs, and assessed by measuring residual DNA, mechanical properties, and key matrix proteins (collagen, elastin, glycosaminoglycans). To study intrinsic matrix biologic cues, human endothelial cells were seeded onto acellular slices and analyzed for markers of cell health and inflammation. Despite similar levels of collagen after decellularization, human and primate lungs were stiffer, contained more elastin, and retained fewer glycosaminoglycans than pig or rat lung scaffolds. Human endothelial cells seeded onto human and primate lung tissue demonstrated less expression of vascular cell adhesion molecule and activation of nuclear factor-κB compared to those seeded onto rodent or porcine tissue. Adhesion of endothelial cells was markedly enhanced on human and primate tissues. Our work suggests that species-dependent biologic cues intrinsic to lung extracellular matrix could have profound effects on attempts at lung regeneration.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA; Department of Anesthesiolgy, Yale University, New Haven, CT, USA.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Balestrini
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Gard
authors.affiliation: Department of Cell Biology, Yale University, New Haven, CT, USA.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Gerhold
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Elise C
authors.initials: EC
authors.lastname: Wilcox
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schwan
authors.affiliation: Department of Anesthesiolgy, Yale University, New Haven, CT, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Le
authors.affiliation: Department of Anesthesiolgy, Yale University, New Haven, CT, USA.
authors.forename: Pavlina
authors.initials: P
authors.lastname: Baevova
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Sashka
authors.initials: S
authors.lastname: Dimitrievska
authors.affiliation: Department of Anesthesiolgy, Yale University, New Haven, CT, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiolgy, Yale University, New Haven, CT, USA.
authors.forename: Sumati
authors.initials: S
authors.lastname: Sundaram
authors.affiliation: Department of Internal Medicine, Yale University, New Haven, CT, USA.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Laure
authors.initials: L
authors.lastname: Rittié
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Dyal
authors.affiliation: Department of Cell Biology and Physiology, Washington University St. Louis, St. Louis, MO, USA.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Broekelmann
authors.affiliation: Department of Cell Biology and Physiology, Washington University St. Louis, St. Louis, MO, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mecham
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA; Department of Cell Biology, Yale University, New Haven, CT, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schwartz
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA; Department of Anesthesiolgy, Yale University, New Haven, CT, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Niklason
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: docew@umich.edu.
authors.forename: Eric S
authors.initials: ES
authors.lastname: White
mesh_terms: D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000032:analysis; D004549:Elastin / Q000032:analysis; D042783:Endothelial Cells / Q000166:cytology*; D005109:Extracellular Matrix / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D008168:Lung / Q000737:chemistry* / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D012038:Regeneration; D044968:Regenerative Medicine; D013552:Swine; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen; D004549:Elastin
keywords: Bioactivity; Decellularization; Extracellular matrix; Lung tissue engineering