Dhawan Lab at the Mowat Labs, Institute of Liver Studies, King's College London at King's College Hospital, London, UK.
Paediatric Liver GI and Nutrition Centre, King's College Hospital, London, UK.
Stem Cells Transl Med. 2024 Mar 15;13(3):204-218. doi: 10.1093/stcltm/szad084.
Orthotopic liver transplantation (OLT) is the current standard of care for both chronic and acute terminal liver disease. However, a major limitation of this treatment is the shortage of healthy donor organs and the need for life-long immunosuppression to prevent graft rejection. Hepatocyte transplantation (HTx) has emerged as a promising, alternative therapeutic approach to either replace OLT or to act as a bridge until a donor liver becomes available thus reducing waiting list mortality. HTx involves the infusion and engraftment of human hepatocytes, typically isolated from organs unsuitable for OLT, into recipient liver parenchyma to carry out the missing hepatic function of the native cells. HTx is less invasive than OLT and can be performed repeatedly if required. The safety of clinical HTx has been shown and treatment results are promising, especially in patients with liver-based metabolic disorders. Nevertheless, HTx has failed to become the standard of care treatment for such disorders. This review aims to evaluate the progress that has been made within the field of HTx over the last 30 years and identify potential shortcomings within the approach which may be hindering its routine clinical application.
原位肝移植(OLT)是治疗慢性和急性终末期肝病的当前标准治疗方法。然而,这种治疗方法的一个主要限制是健康供体器官的短缺和需要终生免疫抑制以防止移植物排斥。肝细胞移植(HTx)作为一种有前途的替代治疗方法已经出现,可以替代 OLT 或作为桥接,直到供体肝脏可用,从而降低等待名单上的死亡率。HTx 涉及将人肝细胞输注和植入受体肝实质中,这些肝细胞通常是从不适合 OLT 的器官中分离出来的,以发挥原生细胞缺失的肝脏功能。HTx 比 OLT 具有更小的侵入性,如果需要,可以重复进行。临床 HTx 的安全性已经得到证实,治疗效果很有前景,特别是在患有基于肝脏的代谢紊乱的患者中。然而,HTx 未能成为此类疾病的标准治疗方法。本综述旨在评估过去 30 年来 HTx 领域取得的进展,并确定该方法中可能阻碍其常规临床应用的潜在缺陷。