Imperial College London
Alternate

DrArmandoDel Rio Hernandez

Faculty of Engineering, Department of Bioengineering

Reader in Cellular and Molecular Mechanotransduction
 
 
 
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Contact

 

+44 (0)20 7594 5187a.del-rio-hernandez

 
 
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Location

 

308Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mazza:2019:10.3390/cells9010083,
author = {Mazza, G and Telese, A and Al-Akkad, W and Frenguelli, L and Levi, A and Marrali, M and Longato, L and Thanapirom, K and Vilia, MG and Lombardi, B and Crowley, C and Crawford, M and Karsdal, MA and Leeming, DJ and Marrone, G and Bottcher, K and Robinson, B and Del, Rio Hernandez A and Tamburrino, D and Spoletini, G and Malago, M and Hall, AR and Godovac-Zimmermann, J and Luong, TV and De, Coppi P and Pinzani, M and Rombouts, K},
doi = {10.3390/cells9010083},
journal = {Cells},
pages = {1--16},
title = {Cirrhotic human liver extracellular matrix 3D scaffolds promote smad-dependent TGF-β1 epithelial mesenchymal transition},
url = {http://dx.doi.org/10.3390/cells9010083},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify and validate new therapeutic targets for HCC. The aim of this work was to validate a new in vitro model based on engineering three-dimensional (3D) healthy and cirrhotic human liver scaffolds with HCC cells recreating the micro-environmental features favoring HCC. Healthy and cirrhotic human livers ECM scaffolds were developed using a high shear stress oscillation-decellularization procedure. The scaffolds bio-physical/bio-chemical properties were analyzed by qualitative and quantitative approaches. Cirrhotic 3D scaffolds were characterized by biomechanical properties and microarchitecture typical of the native cirrhotic tissue. Proteomic analysis was employed on decellularized 3D scaffolds and showed specific enriched proteins in cirrhotic ECM in comparison to healthy ECM proteins. Cell repopulation of cirrhotic scaffolds highlighted a unique up-regulation in genes related to epithelial to mesenchymal transition (EMT) and TGFβ signaling. This was also supported by the presence and release of higher concentration of endogenous TGFβ1 in cirrhotic scaffolds in comparison to healthy scaffolds. Fibronectin secretion was significantly upregulated in cells grown in cirrhotic scaffolds in comparison to cells engrafted in healthy scaffolds. TGFβ1 induced the phosphorylation of canonical proteins Smad2/3, which was ECM scaffold-dependent. Important, TGFβ1-induced phosphorylation of Smad2/3 was significantly reduced and ECM scaffold-independent when pre/simultaneously treated with the TGFβ-R1 kinase inhibitor Galunisertib. In conclusion, the inherent features of cirrhotic human liver ECM micro-environment were dissected and characterized for the first time
AU  - Mazza,G
AU  - Telese,A
AU  - Al-Akkad,W
AU  - Frenguelli,L
AU  - Levi,A
AU  - Marrali,M
AU  - Longato,L
AU  - Thanapirom,K
AU  - Vilia,MG
AU  - Lombardi,B
AU  - Crowley,C
AU  - Crawford,M
AU  - Karsdal,MA
AU  - Leeming,DJ
AU  - Marrone,G
AU  - Bottcher,K
AU  - Robinson,B
AU  - Del,Rio Hernandez A
AU  - Tamburrino,D
AU  - Spoletini,G
AU  - Malago,M
AU  - Hall,AR
AU  - Godovac-Zimmermann,J
AU  - Luong,TV
AU  - De,Coppi P
AU  - Pinzani,M
AU  - Rombouts,K
DO  - 10.3390/cells9010083
EP  - 16
PY  - 2019///
SN  - 2073-4409
SP  - 1
TI  - Cirrhotic human liver extracellular matrix 3D scaffolds promote smad-dependent TGF-β1 epithelial mesenchymal transition
T2  - Cells
UR  - http://dx.doi.org/10.3390/cells9010083
UR  - https://www.mdpi.com/2073-4409/9/1/83
UR  - http://hdl.handle.net/10044/1/75935
VL  - 9
ER  -
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