TY - JOUR

T1 - The human liver matrisome

T2 - Proteomic analysis of native and fibrotic human liver extracellular matrices for organ engineering approaches

AU - Daneshgar, Assal

AU - Klein, Oliver

AU - Nebrich, Grit

AU - Weinhart, Marie

AU - Tang, Peter

AU - Arnold, Alexander

AU - Ullah, Imran

AU - Pohl, Julian

AU - Moosburner, Simon

AU - Raschzok, Nathanael

AU - Strücker, Benjamin

AU - Bahra, Marcus

AU - Pratschke, Johann

AU - Sauer, Igor M.

AU - Hillebrandt, Karl H.

N1 - Funding Information: The authors thank Dr. A. Reutzel-Selke for assistance with statistical analysis and Dr. S.J. Wowro and Dr. G. Tong for assistance with Western blot analysis. We further thank the Einstein Center for Regenerative Therapies for funding this project. Dr. K.H. Hillebrandt is participant in the BIH – Charité Junior Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. PD Dr. B. Strücker and PD Dr. N. Raschzok were participants in the BIH – Charité Clinician Scientist Program funded by the Charité – Universitätsmedizin and the Berlin Institute of Health. The authors acknowledge the support of the Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC 2025.

PY - 2020/10

Y1 - 2020/10

N2 - The production of biomaterials that endow significant morphogenic and microenvironmental cues for the constitution of cell integration and regeneration remains a key challenge in the successful implementation of functional organ replacements. Despite the vast development in the production of biological and architecturally native matrices, the complex compositions and pivotal figures by which the human matrisome mediates many of its essential functions are yet to be defined. Here we present a thorough analysis of the native human liver proteomic landscape using decellularization and defatting protocols to create extracellular matrix scaffolds of natural origin that can further be used in both bottom-up and top-down approaches in tissue engineering based organ replacements. Furthermore, by analyzing human liver extracellular matrices in different stages of fibrosis and cirrhosis, we have identified distinct attributes of these tissues that could potentially be exploited therapeutically and thus require further investigation. The general experimental pipeline presented in this study is applicable to any type of tissue and can be widely used for different approaches in regenerative medicine and in the construction of novel biomaterials for organ engineering approaches.

AB - The production of biomaterials that endow significant morphogenic and microenvironmental cues for the constitution of cell integration and regeneration remains a key challenge in the successful implementation of functional organ replacements. Despite the vast development in the production of biological and architecturally native matrices, the complex compositions and pivotal figures by which the human matrisome mediates many of its essential functions are yet to be defined. Here we present a thorough analysis of the native human liver proteomic landscape using decellularization and defatting protocols to create extracellular matrix scaffolds of natural origin that can further be used in both bottom-up and top-down approaches in tissue engineering based organ replacements. Furthermore, by analyzing human liver extracellular matrices in different stages of fibrosis and cirrhosis, we have identified distinct attributes of these tissues that could potentially be exploited therapeutically and thus require further investigation. The general experimental pipeline presented in this study is applicable to any type of tissue and can be widely used for different approaches in regenerative medicine and in the construction of novel biomaterials for organ engineering approaches.

KW - Acellular tissue scaffold

KW - Bioink

KW - Human liver matrisome

KW - Liver fibrosis

KW - Organ engineering

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=85088750786&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2020.120247

DO - 10.1016/j.biomaterials.2020.120247

M3 - Article

C2 - 32739662

AN - SCOPUS:85088750786

VL - 257

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

M1 - 120247

ER -