Alginate-encapsulated hepatocyte transplantation is a promising strategy to treat liver failure. However, its clinical application was impeded by the lack of primary human hepatocytes and difficulty in controlling their quality. We previously reported proliferating human hepatocytes (ProliHHs). Here, quality-controlled ProliHHs were produced in mass and engineered as liver organoids to improve their maturity. Encapsulated ProliHHs liver organoids (eLO) were intraperitoneally transplanted to treat liver failure animals. Notably, eLO treatment increased the survival of mice with post-hepatectomy liver failure (PHLF) and ameliorated hyperammonemia and hypoglycemia by providing liver functions. Additionally, eLO treatment protected the gut from PHLF-augmented permeability and normalized the increased serum endotoxin and inflammatory response, which facilitated liver regeneration. The therapeutic effect of eLO was additionally proved in acetaminophen-induced liver failure. Furthermore, we performed assessments of toxicity and biodistribution, demonstrating that eLO had no adverse effects on animals and remained non-tumorigenic.

海藻酸盐包裹的肝细胞移植是治疗肝衰竭的一种有前景的策略。然而，由于原代人肝细胞缺乏且质量难以控制，其临床应用受到阻碍。我们之前报道了增殖的人肝细胞（ProliHH）。在这里，大规模生产了质量受控的 ProliHH，并将其设计为肝脏类器官，以提高其成熟度。将封装的 ProliHHs 肝类器官 (eLO) 腹膜内移植以治疗肝功能衰竭动物。值得注意的是，eLO 治疗提高了肝切除后肝衰竭 (PHLF) 小鼠的存活率，并通过提供肝功能改善高氨血症和低血糖。此外，eLO 治疗可保护肠道免受 PHLF 增加的通透性影响，并使增加的血清内毒素和炎症反应正常化，从而促进肝脏再生。 eLO 在对乙酰氨基酚诱发的肝衰竭中的治疗效果也得到了证实。此外，我们还对毒性和生物分布进行了评估，证明 eLO 对动物没有不良影响，并且保持非致瘤性。