Quaglia Alberto, Lehec Sharon C, Hughes Robin D, Mitry Ragai R, Knisely A S, Devereaux Stephen, Richards Julie, Rela Mohamed, Heaton Nigel D, Portmann Bernard C, Dhawan Anil
Institute of Liver Studies, King's College Hospital and King's College London School of Medicine, London, UK.
Cell Transplant. 2008;17(12):1403-14. doi: 10.3727/096368908787648083.
There are limited data regarding donor hepatocyte engraftment into recipient liver after human hepatocyte transplantation (HHTx). We reviewed the explant livers of seven children with metabolic disorders [ornithine-transcarbamylase deficiency (one), coagulation factor VII deficiency (three), Crigler-Najjar syndrome (one), progressive familial intrahepatic cholestasis type 2 (PFIC-2) deficiency (two)] who received allograft hepatocytes by intraportal infusion with improvement in phenotype, although all later underwent liver transplantation (LT). Immunohistochemistry for bile salt export protein (BSEP) in the PFIC-2 patients and genetic typing following laser capture microdissection (LCM) of liver cells in the others were used to identify donor hepatocytes in recipient explant livers. Explant livers usually showed a preserved lobular architecture. In one patient, hepatocytes were identified inside portal vein thrombi. No donor hepatocytes in liver cell plates were identified immunohistochemically or by genetic typing. HHTx was generally followed by partial recovery of metabolic function; the procedure was well tolerated; any increase in portal vein pressure was transient. Hepatocytes were identified in portal vein thrombi, even months after portal vein infusion. Further studies are needed to monitor donor hepatocytes in vivo, to quantify better the efficacy of the procedure and to find ways of improving engraftment and function.
关于人类肝细胞移植(HHTx)后供体肝细胞植入受体肝脏的数据有限。我们回顾了7例患有代谢紊乱疾病儿童的移植肝脏,这些疾病包括鸟氨酸转氨甲酰酶缺乏症(1例)、凝血因子VII缺乏症(3例)、克里格勒-纳贾尔综合征(1例)、2型进行性家族性肝内胆汁淤积症(PFIC-2)缺乏症(2例),他们通过门静脉内输注接受了同种异体肝细胞,尽管之后均接受了肝移植(LT),但其表型均有改善。通过对PFIC-2患者进行胆盐输出蛋白(BSEP)免疫组化,以及对其他患者的肝细胞进行激光捕获显微切割(LCM)后的基因分型,来鉴定受体移植肝脏中的供体肝细胞。移植肝脏通常呈现出保留的小叶结构。在1例患者中,在门静脉血栓内发现了肝细胞。在肝细胞板中未通过免疫组化或基因分型鉴定出供体肝细胞。HHTx后通常会出现代谢功能部分恢复;该操作耐受性良好;门静脉压力的任何升高都是短暂的。即使在门静脉输注数月后,仍在门静脉血栓中发现了肝细胞。需要进一步研究以在体内监测供体肝细胞,更好地量化该操作的疗效,并找到改善植入和功能的方法。