Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine

Jenna L. Balestrini, Ashley L. Gard, Kristin A. Gerhold, Elise C. Wilcox, Angela Liu, Jonas Schwan, Andrew V. Le, Pavlina Baevova, Sashka Dimitrievska, Liping Zhao, Sumati Sundaram, Huanxing Sun, Laure Rittié, Rachel Dyal, Tom J. Broekelmann, Robert P. Mecham, Martin A. Schwartz, Laura E. Niklason, Eric S. White

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish
Pages (from-to)220-230
Number of pages11
JournalBiomaterials
Volume102
DOIs
StatePublished - Sep 1 2016

Keywords

  • Bioactivity
  • Decellularization
  • Extracellular matrix
  • Lung tissue engineering

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