Liver Engineering and Regeneration

Background to the research:

The extracellular matrix of the liver is a complex network of proteins that provides support for the cells. Until recently, this has been thought of as an inactive and inert architectural buttress. Recent evidence suggests that this is instead a very active participant both of regeneration and repair, as well as disease progression and inflammation, with aberrant changes in ECM composition induced in chronic liver disease and cancer.

There is an urgent need for reliable and reproducible methods to understand how the extracellular matrix in different microenvironments influences inflammation and cancer progression as current available models do not mimic the pathogenesis of human liver injury and cancer. Bio-engineered tissues could represent a robust and biologically relevant model, where disease mechanisms and drug testing studies can be investigated.

We develop culture systems using extracellular matrix-derived scaffolds from decellularized tissues seeded with appropriate cell types and cultured in custom bioreactors to provide a more efficient cell-cell and cell-matrix communication. 

We work on generation of novel bio-engineered liver and tumour preparations with structural integrity that exhibits metabolic and immunological functionality as immunocompetent 3D systems. The 3D innovative preparations will reflect specificity of a native tissue, in use in disease modelling, drug screening or regenerative medicine.

In these models, we study the relationship between extracellular matrix and immune system in chronic liver injury and in tumour microenvironments.

 

Head of Group:

Dr Luca Urbani, Principal Investigator, Head of LIver Regeneration & Tissue Engineering Group

Institute of Hepatology, London and Senior Lecturer (Adj), King's College London

Contact:  luca.urbani@researchinliver.org.uk

 

Key collaborators:

Prof Paolo De Coppi, Great Ormond Street Institute of Child Health, UCL; Prof Massimo Pinzani and Dr Giuseppe Mazza, Royal Free Hospital, UCL; Prof Sara Mantero, Politecnico of Milan, Italy; Prof Marco Agostini, University of Padua and Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy; Dr Martina Piccoli, University of Padua and Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy; Dr Roberto Gramignoli, Karolinska Institutet

 

Key publications:

Crowley C, Butler C, Camilli C, Hynds R, Kolluri KK, Janes SM, De Coppi P, Urbani L (2019). Non-invasive longitudinal bioluminescence imaging of human mesoangioblasts in bioengineered esophagi. Tissue Eng Part C Methods. 2019 Feb;25(2):103-113.

Urbani L, Camilli C, Phylactopoulos DE, Crowley C, Natarajan D, Scottoni F,  Maghsoudlou P, McCann CJ, Pellegata AF, Urciuolo A, Deguchi K, Khalaf S, Aruta S, Signorelli MC, Kiely D, Hannon E,  Trevisan M, Wong RR, Baradez MO, Moulding D, Virasami A, Gjinovci A, Loukogeorgakis S, Mantero S, Thapar N, Sebire N, Eaton S, Lowdell M, Cossu G, Bonfanti P, De Coppi P (2018). Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors. Nature Communications 9, Article number: 4286.

Urciuolo A, Urbani L (co-first author), Perin S, Maghsoudlou P, Scottoni F, Gjinovci A, Collins-Hooper H, Loukogeorgakis S, Tyraskis A, Torelli S, Germinario E, Alvarez Fallas ME, Julia-Vilella C, Eaton S, Blaauw B, Patel K, De Coppi P (2018). Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration. Scientific Reports 2018 May 30;8(1):8398.

Alvarez-Fallas ME, Piccoli M, Franzin C, Sgro’ A, Dedja A, Urbani L, Bertin E, Trevisan C, Gamba P, Burns AJ, De Coppi P, Pozzobon M (2018). Decellularized diaphragmatic muscle drives a constructive angiogenic response in vivo. Int J Mol Sci Apr 28: 19(5).

Piccoli M, D’Angelo E, Crotti S, Sensi F, Urbani L, Maghin E, Burns A, De Coppi P, Fassan M, Rugge M, Rizzolio F, Giordano A, Pilati P, Mammano E, Pucciarelli S, Agostini M (2017). Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research. J Cell Physiol. 2017 Dec 15.

Mazza G, Al-Akkad W, Telese A, Longato L, Urbani L, Robinson B, Hall A, Kong K, Frenguelli L, Marrone G, Willacy O, Shaeri M, Burns A, Malago M, Gilbertson J, Rendell N, Moore K, Hughes D, Notingher I, Jell G, Del Rio Hernandez A, De Coppi P, Rombouts K, Pinzani M (2017). Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization. Sci Rep. 2017 Jul 17;7(1):5534.

Urbani L, Maghsoudlou P, Milan A, Menikou M, Hagen CK, Totonelli G, et al. (2017) Long-term cryopreservation of decellularised oesophagi for tissue engineering clinical application. PLoS ONE 12(6): e0179341.

Butler C, Hynds RE, Crowley C, Gowersa KHC, Partington L, Hamilton NJ, Cavalhos C, Platé M, Samuel ER, Burns A, Urbani L, Birchall MA, Lowdellc MW, De Coppi P, Janes MJ (2017). Vacuum-assisted decellularization as an accelerated protocol to generate tissue-engineered human tracheal scaffolds. Biomaterials 2017 Apr;124:95-105.

Maghsoudlou P, Georgiades F, Smith H, Milan A, Shangaris P, Urbani L, Loukogeorgakis SP, Lombardi B, Mazza G, et al (2016). Optimization of liver decellularization maintains extracellular matrix micro-architecture and composition predisposing to effective cell seeding. Plos One 2016 May 9;11(5):e0155324.

Piccoli M, Urbani L (co-first author), Alvarez-Fallas ME, Franzin C, Dedja A, Bertin E, Zuccolotto G, Rosato A, Pavan P, Elvassore N, et al (2016). Improvement of diaphragmatic performance through orthotopic application of decellularized extracellular matrix patch. Biomaterials. 2016 Jan;74:245-55.

Mazza G, Rombouts K, Rennie Hall A, Urbani L, Vinh Luong T, Al-Akkad W, Longato L, Brown D, Maghsoudlou P, Dhillon AP, Fuller B, et al (2015). Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation. Sci Rep. 2015 Aug 7;5:13079.

Peloso A, Urbani L, Cravedi P, Katari R, Maghsoudlou P, Alvarez Fallas ME, Sordi V, Citro C, Purroy C, Niu G, et al (2015). The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-Generation Bioartificial Endocrine Pancreas. ANNSURG-D-15-00175.

Baiguera S, Urbani L, Del Gaudio C (2014). Tissue engineered scaffolds for an effective healing and regeneration: reviewing orthotopic studies. Biomed Res Int. 2014; Epub 2014 Aug 27.

Fishman JM, Lowdell MW, Urbani L, Ansari T, Burns AJ, Turmaine M, North J, Sibbons P, Seifalian AM, Wood KJ, et al (2013). Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model. PNAS Aug 27;110(35):14360-5.

Urbani L, Piccoli M, Franzin C, Pozzobon M and De Coppi P (2012). Hypoxia increases mouse satellite cell clone proliferation maintaining both in vitro and in vivo heterogeneity and myogenic potential. PloS ONE Nov;7(11): e49860.

Published by: Foundation for Liver Research

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