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Preclinical characterization of alginate-Poly-L-Lysine encapsulated HepaRG for extracorporeal liver supply
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  • Mattia Pasqua,
  • Ulysse Pereira,
  • Claire de Lartigue,
  • Jonathan Nicolas,
  • Pascale Vigneron,
  • Quentin Dermigny,
  • Cecile Legallais
Mattia Pasqua
Universite de Technologie de Compiegne
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Ulysse Pereira
Universite de Technologie de Compiegne
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Claire de Lartigue
Universite de Technologie de Compiegne
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Jonathan Nicolas
Universite de Technologie de Compiegne
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Pascale Vigneron
Universite de Technologie de Compiegne
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Quentin Dermigny
Universite de Technologie de Compiegne
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Cecile Legallais
Université de Technologie de Compiègne
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Abstract

We recently demonstrated that HepaRG cells encapsulated into 1.5% alginate beads are capable of self-assembling into spheroids. They adequately differentiate into hepatocyte-like cells, with hepatic features observed at day 14 post-encapsulation required for external bioartificial liver applications. Preliminary investigations performed within a bioreactor under shear stress conditions and using a culture medium mimicking acute liver failure (ALF) highlighted the need to reinforce beads with a polymer coating. We demonstrated in a first step that a Poly-L-Lysine coating improved the mechanical stability, without altering the metabolic activities necessary for bioartificial liver applications (such as ammonia and lactate elimination). In a second step, we tested the optimized biomass in a newly-designed perfused dynamic bioreactor (PDB), in the presence of the medium model for pathological plasma for 6 hours. Performances of the biomass were enhanced as compared to the steady configuration, demonstrating its efficacy in decreasing the typical toxins of ALF. This type of bioreactor is easy to scale up as it relies on the number of micro-encapsulated cells, and could provide an adequate hepatic biomass for liver supply. Its design allows it to be integrated into a hybrid artificial/bioartificial liver setup for further clinical studies regarding its impact on ALF animal models.

Peer review status:ACCEPTED

23 May 2020Submitted to Biotechnology and Bioengineering
23 May 2020Submission Checks Completed
23 May 2020Assigned to Editor
05 Jul 2020Reviewer(s) Assigned
01 Sep 2020Editorial Decision: Revise Minor
01 Sep 2020Review(s) Completed, Editorial Evaluation Pending
15 Sep 20201st Revision Received
16 Sep 2020Submission Checks Completed
16 Sep 2020Assigned to Editor
16 Sep 2020Reviewer(s) Assigned
26 Sep 2020Review(s) Completed, Editorial Evaluation Pending
26 Sep 2020Editorial Decision: Accept