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Quantitative evaluation of long-term liver repopulation and the reconstitution of bile ductules after hepatocellular transplantation

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World Journal of Gastroenterology 2005年第39期11卷 6176-6181页

作者： Yun-Wen Zheng Nobuhiro Ohkohchi Hideki Taniguchi Department of Regenerative Medicine Graduate School of Medical Science Yokohama City University Yokohama 236-0004 Japan Department of Surgery Institute of Clinical Medicine University of Tsukuba Tsukuba 305-8575 Japan Research Unit for Organ Regeneration Center for Developmental Biology RIKEN Kobe 650-0047 Japan

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 too. 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.

关键词： Hepatocellular transplantation Hepatic stem cell Kinetics Cell dose Long-term repopulation Bile ductules Quantification in viva, therapeutic potential

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