Functional Role of Glycosaminoglycans in Decellularized Lung Extracellular Matrix

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Functional Role of Glycosaminoglycans in Decellularized Lung Extracellular Matrix. / Uhl, Franziska; Zhang, Fuming; Pouliot, Robert; Uriarte, Juan Jose; Rolandsson Enes, Sara; Han, Xiaorui; Ouyang, Yilan; Xia, Ke; Westergren-Thorsson, Gunilla; Malmström, Anders; Hallgren, Oskar; Linhardt, Robert J; Weiss, Daniel.

In: Acta Biomaterialia, Vol. 102, 15.01.2020, p. 231-246.

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Uhl, Franziska ; Zhang, Fuming ; Pouliot, Robert ; Uriarte, Juan Jose ; Rolandsson Enes, Sara ; Han, Xiaorui ; Ouyang, Yilan ; Xia, Ke ; Westergren-Thorsson, Gunilla ; Malmström, Anders ; Hallgren, Oskar ; Linhardt, Robert J ; Weiss, Daniel. / Functional Role of Glycosaminoglycans in Decellularized Lung Extracellular Matrix. In: Acta Biomaterialia. 2020 ; Vol. 102. pp. 231-246.

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TY - JOUR

T1 - Functional Role of Glycosaminoglycans in Decellularized Lung Extracellular Matrix

AU - Uhl, Franziska

AU - Zhang, Fuming

AU - Pouliot, Robert

AU - Uriarte, Juan Jose

AU - Rolandsson Enes, Sara

AU - Han, Xiaorui

AU - Ouyang, Yilan

AU - Xia, Ke

AU - Westergren-Thorsson, Gunilla

AU - Malmström, Anders

AU - Hallgren, Oskar

AU - Linhardt, Robert J

AU - Weiss, Daniel

PY - 2020/1/15

Y1 - 2020/1/15

N2 - Despite progress in use of decellularized lung scaffolds in ex vivo lung bioengineering schemes, including use of gels and other materials derived from the scaffolds, the detailed composition and functional role of extracellular matrix (ECM) proteoglycans (PGs) and their glycosaminoglycan (GAG) chains remaining in decellularized lungs, is poorly understood. Using a commonly utilized detergent-based decellularization approach in human autopsy lungs resulted in disproportionate losses of GAGs with depletion of chondroitin sulfate/dermatan sulfate (CS/DS) > heparan sulfate (HS) > hyaluronic acid (HA). Specific changes in disaccharide composition of remaining GAGs were observed with disproportionate loss of NS and NS2S for HS groups and of 4S for CS/DS groups. No significant influence of smoking history, sex, time to autopsy, or age was observed in native vs. decellularized lungs. Notably, surface plasmon resonance demonstrated that GAGs remaining in decellularized lungs were unable to bind key matrix-associated growth factors FGF2, HGF, and TGFβ1. Growth of lung epithelial, pulmonary vascular, and stromal cells cultured on the surface of or embedded within gels derived from decellularized human lungs was differentially and combinatorially enhanced by replenishing specific GAGs and FGF2, HGF, and TGFβ1. In summary, lung decellularization results in loss and/or dysfunction of specific GAGs or side chains significantly affecting matrix-associated growth factor binding and lung cell metabolism. GAG and matrix-associated growth factor replenishment thus needs to be incorporated into schemes for investigations utilizing gels and other materials produced from decellularized human lungs.

AB - Despite progress in use of decellularized lung scaffolds in ex vivo lung bioengineering schemes, including use of gels and other materials derived from the scaffolds, the detailed composition and functional role of extracellular matrix (ECM) proteoglycans (PGs) and their glycosaminoglycan (GAG) chains remaining in decellularized lungs, is poorly understood. Using a commonly utilized detergent-based decellularization approach in human autopsy lungs resulted in disproportionate losses of GAGs with depletion of chondroitin sulfate/dermatan sulfate (CS/DS) > heparan sulfate (HS) > hyaluronic acid (HA). Specific changes in disaccharide composition of remaining GAGs were observed with disproportionate loss of NS and NS2S for HS groups and of 4S for CS/DS groups. No significant influence of smoking history, sex, time to autopsy, or age was observed in native vs. decellularized lungs. Notably, surface plasmon resonance demonstrated that GAGs remaining in decellularized lungs were unable to bind key matrix-associated growth factors FGF2, HGF, and TGFβ1. Growth of lung epithelial, pulmonary vascular, and stromal cells cultured on the surface of or embedded within gels derived from decellularized human lungs was differentially and combinatorially enhanced by replenishing specific GAGs and FGF2, HGF, and TGFβ1. In summary, lung decellularization results in loss and/or dysfunction of specific GAGs or side chains significantly affecting matrix-associated growth factor binding and lung cell metabolism. GAG and matrix-associated growth factor replenishment thus needs to be incorporated into schemes for investigations utilizing gels and other materials produced from decellularized human lungs.

KW - Lung

KW - Decellularization

KW - Glycosaminoglycan

KW - Matrix-associated growth factors

KW - COPD

KW - extracellular matrix gel

UR - https://scopus.com/record/display.uri?eid=2-s2.0-85076542780&origin=inward&txGid

U2 - 10.1016/j.actbio.2019.11.029

DO - 10.1016/j.actbio.2019.11.029

M3 - Article

VL - 102

SP - 231

EP - 246

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1878-7568

ER -