生物人工肝系统治疗肝衰竭的研究进展与展望:从细胞源优化到多靶点协同干预

摘要/Abstract

摘要： 慢加急性肝衰竭(ACLF)病死率极高,肝移植因供体短缺而应用受限,生物人工肝(BAL)系统作为重要的替代治疗手段,历经数十年发展,正从单一功能替代向多靶点协同干预的复合型治疗平台演进。早期以肝癌细胞系HepG2为核心的体外肝脏辅助装置系统虽进入大规模临床试验,但未能提高患者生存率,凸显了功能性肝细胞的重要性。随后,基于直接重编程肝细胞的BAL系统在临床前及Ⅱ期临床试验中展现出治疗潜力,扩增的原代人肝细胞也为BAL系统提供了新的细胞来源。然而,ACLF由肝功能衰竭与全身性炎症反应共同驱动,传统BAL系统对此复合病理机制干预不足。近期,相关研究组提出了通用优化型iHLC串联粒细胞和单核细胞分离术(UTOpiA)系统,将免疫调节柱与干细胞来源肝细胞生物反应器串联集成,该系统在临床前模型中实现了肝脏支持与抗炎治疗的协同,为新一代BAL系统的设计提供了范式转变的路径。展望未来,间充质干细胞介导的体外免疫调控策略有望实现对患者免疫细胞的主动重塑,离体肝脏器官生物人工肝理念则可能从器官层面实现全功能替代。本文系统综述BAL系统的细胞源演进、代表性系统的临床前与临床研究进展,分析从单一功能替代向多靶点协同干预平台发展的科学逻辑与关键挑战,旨在为BAL系统的优化与临床转化提供参考。

关键词: 生物人工肝, 慢加急性肝衰竭, 干细胞, 免疫调节, 离体器官灌注, 临床转化

陈雅丽, 吴泽双, 田沂. 生物人工肝系统治疗肝衰竭的研究进展与展望:从细胞源优化到多靶点协同干预[J]. 肝脏, 2026, 31(3): 316-321.

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