Bone marrow-derived liver stem cell and mature hepatocyte engraftment in livers undergoing rejection
Bone marrow-derived liver stem cell and mature hepatocyte engraftment in livers undergoing rejection
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DOI：
10.1067/msy.2002.125785
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发表时间：
2002-08-01
期刊：
影响因子：
3.8
通讯作者：
Muraca, M
中科院分区：
文献类型：
--
作者：
Avital, I;Feraresso, C;Muraca, M
背景资料。终末期肝病的最终治疗方法是原位肝移植(OLT)。然而，排斥反应仍然是原位肝移植术后死亡率和发病率的主要原因。肝细胞移植已被实验性地用于治疗肝病。本研究的目的是探讨骨髓来源的肝干细胞(BDLSC)和成熟肝细胞能否在排斥反应后的移植肝中再生。从D‘agti(C3阳性雌性)大鼠开始对Lewis(C3阴性雌性)大鼠进行OLT。将雄性Lewis大鼠的BDLSC移植到D‘agti(雌性)大鼠的肝脏内。A组(n=9)门静脉注射生理盐水。B组(n=9)和C组(n=9)分别行门脉内移植成熟肝细胞(Lewis女，0.75×10(7))和DBLSC(Lewis男，5×10(4))。各组均给予亚治疗性免疫抑制(环孢素0.25 mg/kg/d)，共13d。用免疫组织化学(C3抗原阴性细胞)、原位杂交(Y染色体阳性的BDLSC)和组织学(苏木精-伊红染色)检测肝移植后的排斥反应。BDLSC和成熟肝细胞分别回填了62+/-12.3%和2.5+/-1.7%的排斥肝。BDLSC显示，肝小叶和门脉三联征形成较少。停用免疫抑制药物36天后出现排斥反应的证据。BDLSC可以使发生严重排斥反应的肝脏再生。此外，BDLSC还可以分化为肝细胞和胆管细胞。这一发现可能具有重要的临床意义。
Background. The definitive therapy,for end-stage liver disease is orthotopic liver transplantation (OLT). However, rejection is still a major cause of mortality and morbidity following OLT. Hepatocyte transplantation has been used experimentally to treat liver diseases. The aim of this study was to investigate whether bone marrow-derived liver stem cells (BDLSC) and mature hepatocytes could repopulate transplanted livers undergoing rejection.Methods. OLT was carried out from D'Agouti (C3-positive female) into Lewis (C3-negative female) rats. BDLSC were transplanted from Lewis (male) into livers of D'Agouti (female) rats. Group A (n = 9) received intraportal normal saline. Groups B (n = 9) and C (n = 9) underwent intraportal transplantation of mature hepatocytes (Lewis female, 0.75 X 10(7)) and DBLSC (Lewis male, 5 X 10(4)) respectively. All groups received subtherapeutic immunosuppression (Cyclosporin 0.25 mg/kg/d) for 13 days. Liver repopulation was assessed using immunohistochemistry (C3 antigen-negative cells), in-situ hybridization, (Y-chromosome positive BDLSC) and histologic assessment (hematoxylin and eosin) for rejection.Results. BDLSC and mature hepatocytes repopulated 62 +/- 12.3% and 2.5 +/- 1.7% of rejecting livers, respectively. BDLSC demonstrated,formation of hepatic lobules and portal triads with little. evidence of rejection 36 days after discontinuation of immunosuppression.Conclusions. BDLSC can repopulate livers undergoing severe rejection. Moreover BDLSC can differentiate into hepatocytes and cholangiocytes. This finding may have important clinical implications.