TY - JOUR
T1 - Comparative biology of decellularized lung matrix
T2 - Implications of species mismatch in regenerative medicine
AU - Balestrini, Jenna L.
AU - Gard, Ashley L.
AU - Gerhold, Kristin A.
AU - Wilcox, Elise C.
AU - Liu, Angela
AU - Schwan, Jonas
AU - Le, Andrew V.
AU - Baevova, Pavlina
AU - Dimitrievska, Sashka
AU - Zhao, Liping
AU - Sundaram, Sumati
AU - Sun, Huanxing
AU - Rittié, Laure
AU - Dyal, Rachel
AU - Broekelmann, Tom J.
AU - Mecham, Robert P.
AU - Schwartz, Martin A.
AU - Niklason, Laura E.
AU - White, Eric S.
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Bioactivity
KW - Decellularization
KW - Extracellular matrix
KW - Lung tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=84975887110&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2016.06.025
DO - 10.1016/j.biomaterials.2016.06.025
M3 - Article
C2 - 27344365
AN - SCOPUS:84975887110
VL - 102
SP - 220
EP - 230
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
ER -