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Biomaterials. 2016 Sep;102:220-30. doi: 10.1016/j.biomaterials.2016.06.025. Epub 2016 Jun 16.

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

Author information

1
Department of Biomedical Engineering, Yale University, New Haven, CT, USA; Department of Anesthesiolgy, Yale University, New Haven, CT, USA.
2
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
3
Department of Cell Biology, Yale University, New Haven, CT, USA.
4
Department of Anesthesiolgy, Yale University, New Haven, CT, USA.
5
Department of Internal Medicine, Yale University, New Haven, CT, USA.
6
Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
7
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
8
Department of Cell Biology and Physiology, Washington University St. Louis, St. Louis, MO, USA.
9
Department of Biomedical Engineering, Yale University, New Haven, CT, USA; Department of Cell Biology, Yale University, New Haven, CT, USA.
10
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.

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.

KEYWORDS:

Bioactivity; Decellularization; Extracellular matrix; Lung tissue engineering

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