Quantitative evaluation of long-term liver repopulation and the reconstitution of bile ductules after hepatocellular transplantation
Quantitative evaluation of long-term liver repopulation and the reconstitution of bile ductules after hepatocellular transplantation
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DOI：
10.3748/wjg.v11.i39.6176
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发表时间：
2005-10-21
影响因子：
4.3
通讯作者：
Taniguchi, Hideki
中科院分区：
文献类型：
--
作者：
Zheng, Yun-Wen;Ohkohchi, Nobuhiro;Taniguchi, Hideki
目的：供肝短缺严重限制了肝病的治疗。为了解决这一日益严重的问题，肝细胞移植(HTX)作为整个器官移植的替代方案受到了极大的关注。然而，移植细胞的扩增处于低水平，功能肝组织的重建受到这种细胞特性的限制。我们建立了一种动物模型，以更好地了解细胞剂量效应和HTx后肝脏再生的动力学。方法：将DPPIV基因缺陷的大鼠接受逆转录病毒治疗并接受肝部分切除后，输注DPPIV阳性的肝细胞。给大鼠注射不同数量的供体肝细胞，低至100个细胞，在不同的时间点观察肝脏再生情况，直至20mo。结果：移植的肝细胞经历了多轮增殖，并在20mo和所有细胞剂量下稳定地重新植入受损的肝脏。移植细胞在输液后3个月内分裂14次，肝脏再生在3~20个月达到高峰。发生了大约90%的更换。供体来源的细胞也重建了受体的胆管。结论：移植的肝细胞能够完全重建受损的肝脏，这为进一步研究HTX的临床潜力提供了有力的支持。此外，观察到移植的肝细胞也构成胆道系统的组成部分，这表明这些细胞可能具有干细胞的双潜能特性。(C)2005年WJG Press和Elsevier Inc.保留所有权利。
AIM: The treatment of liver disease is severely limited by a shortage of donor livers. In trying to address this growing problem, hepatocellular transplantation (HTx) has received much attention as an alternative to whole organ transplant. However, the expansion of transplanted cells is at low level, and the reconstitution of functional liver tissue is limited by this cellular property. We set up an animal model to better understand cell dose effect and the kinetics of liver repopulation following HTx.METHODS: Dipeptidyl peptidase IV (DPPIV)-deficient rats treated with retrorsine and subjected to partial hepatectomy were infused with DPPIV-positive hepatocytes. Rats were injected with varying numbers of donor hepatocytes down to 100 cells low, and liver repopulation was examined at different time points up to 20 mo long. Repopulation was assessed by computer-aided quantitative detection.RESULTS: Transplanted hepatocytes underwent multiple rounds of proliferation and stably repopulated the injured livers after 20 mo and at all cell doses. Transplanted cells divided 14 times within the 3-mo time period following infusion, and the liver repopulation reached a plateau between 3 and 20 mo. Approximately 90% replacement occurred. Donor-derived cells also reconstituted the bile ductules of the recipients.CONCLUSION: The ability of transplanted hepatocytes to fully reconstitute injured livers strongly supports further investigation into the clinical potential of HTx. Additionally, the observation that transplanted hepatocytes also form components of the biliary system suggests that these cells may have bi-potential property of the stem cells. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.