浙江大学医学院蔡秀军、中科院分子细胞科学卓越创新中心惠利健、Ludi Zhang团队合作的研究表明转分化肝细胞生物人工肝可用于治疗肝衰竭。相关论文于2023年4月13日发表在《细胞—干细胞》杂志上。

研究人员设计了一种临床级生物人工肝（BAL）设备，可在GMP条件下产生人诱导肝细胞（hiHeps）。在猪肝切除手术后肝衰竭（PHLF）模型中，hiHep-BAL处理具有显著的生存优势。除了支持功能外，hiHep-BAL治疗还恢复了残余的肝脏功能，特别是氨解毒功能并促进了肝脏再生。

值得注意的是，一项由研究者发起的对七名延长肝切除患者的研究表明，hiHep-BAL治疗耐受性良好，并且与肝功能和肝再生改善有关，满足安全性和可行性主要终点。这些令人鼓舞的结果值得进一步测试hiHep-BAL在PHLF的应用，其成功将扩大符合肝切除条件的患者群体。

据介绍，肝切除术是原发性肝癌的一线治疗方法，其具有治愈肝癌的潜力。然而，对PHLF的担忧限制了该方法在符合条件患者群体的应用，PHLF是肝切除术后造成死亡的主要原因。

附：英文原文

Title: Reversal of liver failure using a bioartificial liver device implanted with clinical-grade human-induced hepatocytes

Author: Yifan Wang, Qiang Zheng, Zhen Sun, Chenhua Wang, Jin Cen, Xinjie Zhang, Yan Jin, Baihua Wu, Tingting Yan, Ziyuan Wang, Qiuxia Gu, Xingyu Lv, Junjie Nan, Zhongyu Wu, Wenbin Sun, Guoyu Pan, Ludi Zhang, Lijian Hui, Xiujun Cai

Issue&Volume: 2023-04-13

Abstract: Liver resection is the first-line treatment for primary liver cancers, providing the potential for a cure. However, concerns about post-hepatectomy liver failure (PHLF), a leading cause of death following extended liver resection, have restricted the population of eligible patients. Here, we engineered a clinical-grade bioartificial liver (BAL) device employing human-induced hepatocytes (hiHeps) manufactured under GMP conditions. In a porcine PHLF model, the hiHep-BAL treatment showed a remarkable survival benefit. On top of the supportive function, hiHep-BAL treatment restored functions, specifically ammonia detoxification, of the remnant liver and facilitated liver regeneration. Notably, an investigator-initiated study in seven patients with extended liver resection demonstrated that hiHep-BAL treatment was well tolerated and associated with improved liver function and liver regeneration, meeting the primary outcome of safety and feasibility. These encouraging results warrant further testing of hiHep-BAL for PHLF, the success of which would broaden the population of patients eligible for liver resection.

DOI: 10.1016/j.stem.2023.03.013

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00084-X