Ortuño-Costela M Carmen, Pinzani Massimo, Vallier Ludovic
Berlin Institute of Health, BIH Centre for Regenerative Therapies, Charité-Universitätsmedizin, Berlin, Germany.
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Nat Rev Gastroenterol Hepatol. 2025 May;22(5):329-342. doi: 10.1038/s41575-025-01050-2. Epub 2025 Mar 18.
The liver fulfils a plethora of vital functions and, due to their importance, liver dysfunction has life-threatening consequences. Liver disorders currently account for more than two million deaths annually worldwide and can be classified broadly into three groups, considering their onset and aetiology, as acute liver diseases, inherited metabolic disorders and chronic liver diseases. In the most advanced and severe forms leading to liver failure, liver transplantation is the only treatment available, which has many associated drawbacks, including a shortage of organ donors. Cell therapy via fully mature cell transplantation is an advantageous alternative that may be able to restore a damaged organ's functionality or serve as a bridge until regeneration can occur. Pioneering work has shown that transplanting adult hepatocytes can support liver recovery. However, primary hepatocytes cannot be grown extensively in vitro as they rapidly lose their metabolic activity. Therefore, different cell sources are currently being tested as alternatives to primary cells. Human pluripotent stem cell-derived cells, chemically induced liver progenitors, or 'liver' organoids, hold great promise for developing new cell therapies for acute and chronic liver diseases. This Review focuses on the advantages and drawbacks of distinct cell sources and the relative strategies to address different therapeutic needs in distinct liver diseases.
肝脏具有众多重要功能，因其重要性，肝功能障碍会带来危及生命的后果。目前，肝脏疾病在全球每年导致超过200万人死亡，根据发病情况和病因，大致可分为三类，即急性肝病、遗传性代谢紊乱和慢性肝病。在导致肝衰竭的最晚期和最严重形式中，肝移植是唯一可用的治疗方法，但它有许多相关缺点，包括器官供体短缺。通过完全成熟细胞移植进行的细胞治疗是一种有利的替代方法，可能能够恢复受损器官的功能，或在再生发生之前起到桥梁作用。开创性工作表明，移植成人肝细胞可支持肝脏恢复。然而，原代肝细胞在体外不能大量培养，因为它们会迅速丧失代谢活性。因此，目前正在测试不同的细胞来源作为原代细胞的替代物。人多能干细胞衍生的细胞、化学诱导的肝祖细胞或“肝脏”类器官，在开发针对急性和慢性肝病的新细胞疗法方面具有巨大潜力。本综述重点关注不同细胞来源的优缺点，以及针对不同肝病满足不同治疗需求的相关策略。
