Liver from bone marrow in humans
Liver from bone marrow in humans
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DOI：
10.1053/jhep.2000.9124
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发表时间：
2000-07-01
期刊：
影响因子：
13.5
通讯作者：
Krause, DS
中科院分区：
文献类型：
--
作者：
Theise, ND;Nimmakayalu, M;Krause, DS
动物模型显示肝细胞和胆管细胞可以来源于骨髓细胞。我们已经调查了这样的过程是否发生在人类身上。从2名男性供体治疗性骨髓移植的女性受者和4名女性供体原位肝移植的男性受者中获得了档案尸检和活检肝脏标本，用单克隆抗体CAM5.2进行免疫组织化学染色，特异性针对细胞角蛋白8、18和19，在所有组织中对肝细胞、胆管细胞和导管反应进行了典型的强染色，排除了所有非上皮细胞。系统地拍摄载玻片，然后用荧光原位杂交（FISH）对X和Y染色体进行抑制。使用形态学标准，将荧光图像与先前的显微照片逐场比较，以及通过FISH蛋白酶消化持续的二氨基苯二苯（DAB）染色，可以在男性对照肝组织和所有研究标本中鉴定出y阳性肝细胞和胆管细胞。细胞计数根据男性对照肝脏中y阳性细胞的数量进行调整，以纠正3微米薄组织切片中细胞核的部分采样。在研究标本中，调整后的y阳性肝细胞和胆管细胞的植入率分别为4%至43%和4%至38%，其中一个肝移植受者的肝纤维化胆汁淤积性丙型肝炎复发病例中发现了峰值。因此，我们表明，在人类中，肝细胞和胆管细胞可以来自肝外循环干细胞，可能来自骨髓。这种“转分化”可以补充大量的肝实质细胞。
It has been shown in animal models that hepatocytes and cholangiocytes can derive from bone marrow cells. We have investigated whether such a process occurs in humans. Archival autopsy and biopsy liver specimens were obtained from 2 female recipients of therapeutic bone marrow transplantations with male donors and from 4 male recipients of orthotopic liver transplantations from female donors, Immunohistochemical staining with monoclonal antibody CAM5.2, specific for cytokeratins 8, 18, and 19, gave typical strong staining of hepatocytes, cholangiocytes, and ductular reactions in all tissues, to the exclusion of all nonepithelial cells. Slides were systematically photographed and then restained by fluorescence in situ hybridization (FISH) for X and Y chromosomes. Using morphologic criteria, field-by-field comparison of the fluorescent images with the prior photomicrographs, and persistence of the diaminiobenzidene (DAB) stain through the FISH protease digestion, Y-positive hepatocytes and cholangiocytes could be identified in male control liver tissue and in all study specimens. Cell counts were adjusted based on the number of Y-positive cells in the male control liver to correct for partial sampling of nuclei in the 3-micron thin tissue sections. Adjusted Y-positive hepatocyte and cholangiocyte engraftment ranged from 4% to 43% and from 4% to 38%, respectively, in study specimens, with the peak values being found in a case of fibrosing cholestatic recurrent hepatitis C in one of the liver transplant recipients, We therefore show that in humans, hepatocytes and cholangiocytes can be derived from extrahepatic circulating stem cells, probably of bone marrow origin, and such "transdifferentiation" can replenish large numbers of hepatic parenchymal cells.