老挝黄金赌场分子细胞科学卓越创新中心惠利健团队，完成了微囊化可增殖人肝细胞类器官用于肝衰治疗的临床前疗效和安全性评估。2024年3月7日，《细胞—干细胞》杂志在线发表了这项成果。

研究人员表示，海藻酸钠包裹肝细胞移植是治疗肝功能衰竭的一种很有前景的策略。然而，由于缺乏原代人类肝细胞且难以控制其质量，其临床应用受到了阻碍。研究人员曾报道过可增殖的人肝细胞（ProliHH）。

研究人员批量生产了质量可控的ProliHH，并将其设计为肝脏类器官，以提高其成熟度。封装的ProliHH肝脏类器官（eLO）被腹腔移植治疗肝衰竭动物。值得注意的是，eLO治疗提高了肝切除术后肝衰竭（PHLF）小鼠的存活率，并通过提供肝功能改善了高氨血症和低血糖症。

此外，eLO还能保护肠道免受PHLF导致的渗透性增强的影响，并使增加的血清内毒素和炎症反应恢复正常，从而促进肝脏再生。在对乙酰氨基酚诱导的肝衰竭中，eLO的治疗效果也得到了证实。此外，研究人员还对毒性和生物分布进行了评估，结果表明eLO对动物没有不良影响，也不会致癌。

附：英文原文

Title: Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure

Author: Xiang Yuan, Jingqi Wu, Zhen Sun, Jin Cen, Yajing Shu, Chenhua Wang, Hong Li, Dongni Lin, Kun Zhang, Baihua Wu, Anil Dhawan, Ludi Zhang, Lijian Hui

Issue&Volume: 2024-03-07

Abstract: 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.

DOI: 10.1016/j.stem.2024.02.005

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00048-1