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 1.5% alginate beads without preforming spheroids. Starting from a given hepatic biomass, we analyzed cell differentiation and metabolic performance for further use in a fluidized-bed BAL. We observed that cells self-rearranged as aggregates within the beads and adequately differentiated over time, in the absence of any differentiating factors classically used. On day 14 postencapsulation, cells displayed a wide range 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).

中文翻译：

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海藻酸盐珠中的HepaRG自组装球体可满足生物人工肝的临床需求。

在肝组织工程中，现在已经认识到球体中的细胞培养可以促进肝功能的维持。然而，导致球状体形成的过程是费时的，昂贵的并且不易于扩大规模以进一步用于人类生物人工肝（BAL）应用。在这项研究中，我们将HepaRG细胞（肝细胞样细胞的前体）封装在1.5％的藻酸盐珠中，而没有形成球体。从给定的肝脏生物质开始，我们分析了细胞分化和代谢性能，以进一步用于流化床BAL中。我们观察到，在没有经典使用的任何区分因素的情况下，细胞会以小珠内的聚集体形式自我重新排列，并随时间充分分化。在封装后的第14天，细胞显示出广泛的肝功能，对于急性肝衰竭患者的治疗是必需的。这些活动包括白蛋白的合成，氨和乳酸的解毒，以及涉及异种生物代谢的酶（例如CYP1A1 / 2）的功效。