HepaRG Self-Assembled Spheroids in Alginate Beads Meet the Clinical Needs for Bioartificial Liver
Résumé
In liver tissue engineering, cell culture in spheroids is now well
recognized to promote the maintenance of hepatic functions. However,
the process leading to spheroids formation is time consuming, costly,
and not easy to scale-up for further use in human bioartificial liver (BAL)
applications. In this study, we encapsulated HepaRG cells (precursors of
hepatocyte-like cells) in alginate 1.5% without pre-forming spheroids.
Starting from a given hepatic biomass, we analysed cell differentiation
and metabolic performance for further use in fluidized-bed BAL. We
observed that cells rearranged as aggregates into the beads and
adequately differentiated over time, in the absence of any differentiating
factors classically used. At day 14 post-encapsulation, cells displayed a large set of hepatic features necessary for the treatment of a patient in
acute liver failure. These activities include albumin synthesis, ammonia
and lactate detoxification and the efficacy of the enzymes involved in the
xenobiotic metabolism (such as CYP1A1/2).
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