Liver Engineering and Regeneration

Background to the research:

There is an urgent need for reliable and reproducible methods to understand liver diseases as current available models do not mimic the pathogenesis of human liver injury and disease progression. Bioengineered liver tissues could represent a robust and biologically relevant hepatic model, where disease mechanisms and drug testing studies can be investigated.

We work on the generation of a novel bioengineered liver preparation with structural integrity that exhibits metabolic and immunological functionality as a dynamic immunocompetent 3D system for disease modelling and liver regeneration.

The tissue engineering approach to fabricate the bioengineered liver tissue combines i) a natural-derived scaffold, obtained through decellularization; ii) a mix of human primary hepatic cells and iii) a customised bioreactor for the support of cell survival. The 3D system will also include the innate intrahepatic immune system, using perfusion of immune cells through the vasculature of the bioengineered preparation.

The 3D innovative preparation will reflect specificity of a native tissue, in use in disease modelling, drug screening or regenerative medicine.

 

Contact Dr Luca Urbani: 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

 

Key publications:

  1. 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, in press. 
  2. Urbani L, Urciuolo A, 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
  3. Urbani L, Maghsoudlou P, Milan A, Menikou M, Hagen CK, Totonelli G, Camilli C, Eaton S, Burns A, Olivo A, De Coppi P (2017). Long-term cryopreservation of decellularised oesophagi for tissue engineering clinical application. PLoS ONE 12(6): e0179341.
  4. 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. PMCID: PMC4861300.
  5. Urbani L, Piccoli M, 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. PMID: 26461117 DOI: 10.1016/j.biomaterials.2015.10.005.
  6. Mazza G, Rombouts K, Rennie Hall A, Urbani L, Vinh Luong T, Al-Akkad W, Longato L, Brown D, Maghsoudlou P, et al (2015). Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation. Sci Rep. 2015 Aug 7;5:13079. PMCID: PMC4528226.
  7. 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. PMCID: PMC3761636.
  8. 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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