Unidad de Hepatología Experimental, Centro de Investigación, Hospital La Fe, Valencia, Spain.
Cell Transplant. 2010;19(1):21-8. doi: 10.3727/096368909X474267.
The first indication of hepatocyte transplantation is inborn liver-based metabolic disorders. Among these, urea cycle disorders leading to the impairment to detoxify ammonia and Crigler-Najjar Syndrome type I, a deficiency in the hepatic UDP-glucuronosyltransferase 1A1 present the highest incidence. Metabolically qualified human hepatocytes are required for clinical infusion. We proposed fast and sensitive procedures to determine their suitability for transplantation. For this purpose, viability, attachment efficiency, and metabolic functionality (ureogenic capability, cytochrome P450, and phase II activities) are assayed prior to clinical cell infusion to determine the quality of hepatocytes. Moreover, the evaluation of urea synthesis from ammonia and UDP-glucuronosyltransferase 1A1 activity, a newly developed assay using beta-estradiol as substrate, allows the possibility of customizing cell preparation for receptors with urea cycle disorders or Crigler-Najjar Syndrome type I. Sources of human liver and factors derived from the procurement of the liver sample (warm and cold ischemia) have also been investigated. The results show that grafts with a cold ischemia time exceeding 15 h and steatosis should not be accepted for hepatocyte transplantation. Finally, livers from non-heart-beating donors are apparently a potential suitable source of hepatocytes, which could enlarge the liver donor pool.
肝细胞移植的第一个适应证是先天性肝脏代谢紊乱。其中，导致氨解毒功能受损的尿素循环障碍和先天性非溶血性高胆红素血症 I 型（Crigler-Najjar 综合征）的发病率最高，这两种疾病均缺乏肝 UDP-葡糖醛酸基转移酶 1A1。临床输注需要代谢功能正常的人肝细胞。我们提出了快速而敏感的程序来确定其用于移植的适宜性。为此，在临床细胞输注前测定其活力、附着效率和代谢功能（成尿素能力、细胞色素 P450 和 II 相活性），以确定肝细胞的质量。此外，使用雌二醇作为底物的新开发的测定法评估尿素合成从氨和 UDP-葡糖醛酸基转移酶 1A1 活性，为患有尿素循环障碍或先天性非溶血性高胆红素血症 I 型的受体定制细胞制剂成为可能。还研究了人肝的来源和从肝样本采集（热缺血和冷缺血）产生的因素。结果表明，冷缺血时间超过 15 小时和脂肪变性的移植物不应用于肝细胞移植。最后，心脏死亡供体的肝脏显然是肝细胞的潜在合适来源，可以扩大肝供体库。
