Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Liver Transpl. 2010 Aug;16(8):974-82. doi: 10.1002/lt.22099.
Human hepatocyte transplantation is an alternative treatment for acute liver failure and liver diseases involving enzyme deficiencies. Although it has been successfully applied in selected recipients, both isolation and transplantation outcomes have the potential to be improved by better donor selection. This study assessed the impact of various donor variables on isolation outcomes (yield and viability) and posttransplant engraftment, using the SCID/Alb-uPA (severe combined immunodeficient/urokinase type plasminogen activator under the control of an albumin promoter) human liver chimeric mouse model. Human hepatocytes were obtained from 90 human liver donor specimens and were transplanted into 3942 mice. Multivariate analysis revealed improved viability with younger donors (P = 0.038) as well as with shorter warm ischemic time (P = 0.012). Hepatocyte engraftment, assessed by the posttransplant level of serum human alpha1-antitrypsin, was improved with shorter warm ischemia time. Hepatocytes isolated from older donors (>or=60 years) had lower viability and posttransplant engraftment (P <or= 0.01). In conclusion, the selection of young donors (<60 years) and rapid liver specimen retrieval, allowing for shorter warm ischemia time, are key determinants for the success of both the isolation of high viability human hepatocytes and their subsequent posttransplantation capacity for engraftment and expansion.
人肝细胞移植是治疗急性肝功能衰竭和涉及酶缺乏的肝脏疾病的一种替代疗法。虽然它已成功地应用于某些受者，但通过更好的供者选择，分离和移植结果都有可能得到改善。本研究采用 SCID/Alb-uPA（受白蛋白启动子控制的尿激酶型纤溶酶原激活剂的严重联合免疫缺陷）人肝嵌合鼠模型，评估了各种供者变量对分离结果（产率和活力）和移植后植入的影响。从 90 个人类肝脏供体标本中获得人肝细胞，并移植到 3942 只小鼠中。多变量分析显示，年轻供体（P = 0.038）和较短的热缺血时间（P = 0.012）可提高活力。通过移植后血清人α1-抗胰蛋白酶水平评估的肝细胞植入，随着热缺血时间的缩短而得到改善。来自年龄较大供体（>或=60 岁）的肝细胞活力和移植后植入较低（P <或=0.01）。总之，选择年轻供体（<60 岁）和快速获取肝脏标本，以允许较短的热缺血时间，是成功分离高活力人肝细胞及其随后移植后植入和扩增能力的关键决定因素。
