Extensive chimerism in liver transplants: Vascular endothelium, bile duct epithelium, and hepatocytes

Extensive chimerism in liver transplants: Vascular endothelium, bile duct epithelium, and hepatocytes
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DOI:
10.1053/jlts.2003.50116
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发表时间:
2003-06-01
影响因子:
4.6
通讯作者:
Lagaaij, EL
Lagaaij, EL
中科院分区:
医学2区
文献类型:
--
作者:
ten Hove, WR;van Hoek, B;Lagaaij, EL

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移植的肝脏已被证明特别能够诱导耐受性。一种解释可能是嵌合体的存在。任何实体器官移植后,供体来源的细胞都可在受体组织中发现。在移植的肝脏中存在受体来源的细胞的证据非常有限。我们研究了受体来源的非淋巴样细胞是否可以在人肝移植物中找到。研究了5例接受女性供体肝移植的男性患者和11例接受HLA-1不匹配肝移植的患者。我们用两种不同的技术结合双染色技术证实了我们的观察结果。为了识别女性肝移植中的雄性细胞,我们使用性染色体原位杂交技术。为了识别受体来源的特异性HLA I类抗原,我们使用了HLA I类特异性抗体的免疫组织化学。进行双重染色以区分不同的细胞谱系和炎性细胞。在16个供体肝脏中的14个中发现了受体来源的内皮细胞。16例中5例可见受体源性胆管上皮细胞。在研究的5个性别不匹配的供体肝脏中,仅在1个中观察到受体来源的肝细胞。我们的研究提供了证据表明,受体来源的细胞可以取代人肝移植物中的胆管上皮细胞,内皮细胞和肝细胞。这与循环多能祖细胞存在的概念一致,其能够分化成内皮细胞、上皮细胞和肝细胞。
The transplanted liver has been shown to be particularly capable of inducing tolerance. An explanation may be the presence of chimerism. Cells of donor origin have been found in recipient tissues after transplantation of any solid organ. Evidence for the presence of cells of recipient origin within the transplanted liver is very limited. We investigated whether nonlymphoid cells of recipient origin can be found within human liver allografts. Five male patients who received a liver transplant from a female donor and 11 patients who received an HLA-1 mismatched liver transplant were studied. We confirmed our observations with two different techniques in combination with double-staining techniques. To identify male cells in female liver transplants, we used in situ hybridization for sex chromosomes. To identify specific HLA class I antigens of recipient origin, we used immunohistochemistry with HLA class I-specific antibodies. Double staining was performed to discriminate different cell lineages and inflammatory cells. Endothelial cells of recipient origin were found in 14 of 16 donor livers. Bile duct epithelial cells of recipient origin were found in 5 of 16 cases. Hepatocytes of recipient origin were seen in only 1 of the 5 studied sex-mismatched donor livers. Our study provides evidence that cells of recipient origin can replace biliary epithelial cells, endothelial cells, and hepatocytes within the human liver allograft. This is consistent with the concept that circulating pluripotent progenitor cells exist, capable of differentiating into endothelial cells, epithelial cells, and hepatocytes.