Forbes Stuart J, Russo Francesco P, Rey Virginia, Burra Patrizia, Rugge Massimo, Wright Nicholas A, Alison Malcolm R
Hepatology Section, Department of Medicine, Imperial College, London, England.
Gastroenterology. 2004 Apr;126(4):955-63. doi: 10.1053/j.gastro.2004.02.025.
BACKGROUND & AIMS: Myofibroblasts of bone marrow origin have recently been found in a number of parenchymal organs such as the gut and kidney. We have analyzed the origin of myofibroblasts within fibrotic liver in 2 scenarios: (1) 7 male patients (hepatitis B; hepatitis B and D; Wilson's disease; hepatitis B, D, and C; and 3 with hepatitis C) who received liver transplants from female donors and subsequently developed liver fibrosis and (2) a female patient who received a bone marrow transplant from a male donor and subsequently developed hepatitis C-induced cirrhosis.
Through the use of in situ hybridization for the Y chromosome, we have tracked male cells of extrahepatic origin. The phenotype of these male cells was examined by immunohistochemistry using a panel of antibodies against alpha-smooth muscle actin (alpha SMA), vimentin, fibulin-2, and leukocyte common antigen (CD45). Confocal microscopy was performed to confirm the location of the Y chromosome probe within the myofibroblast nuclei.
Significant numbers of Y chromosome-positive cells in fibrotic areas were found to be positive for alpha-SMA, vimentin, and fibulin-2 and negative for CD45, thus having a myofibroblast phenotype. In the liver transplant cases, 6.8%-22.2% of alpha-SMA-positive myofibroblasts contained the Y chromosome. In the female recipient of a bone marrow transplant from a male donor, 12.4% of the myofibroblasts were Y chromosome positive, indicating a bone marrow origin.
There is a significant contribution to liver cirrhosis in humans from extrahepatically derived myofibroblasts in liver disease of diverse etiology.
最近在肠道和肾脏等多种实质器官中发现了骨髓来源的肌成纤维细胞。我们分析了两种情况下纤维化肝脏中肌成纤维细胞的起源：（1）7名男性患者（乙型肝炎；乙型和丁型肝炎；威尔逊病；乙型、丁型和丙型肝炎；以及3名丙型肝炎患者）接受了女性供体的肝脏移植，随后发生肝纤维化；（2）一名女性患者接受了男性供体的骨髓移植，随后发生丙型肝炎诱导的肝硬化。
通过对Y染色体进行原位杂交，我们追踪了肝外来源的男性细胞。使用一组针对α-平滑肌肌动蛋白（α-SMA）、波形蛋白、纤连蛋白-2和白细胞共同抗原（CD45）的抗体，通过免疫组织化学检查这些男性细胞的表型。进行共聚焦显微镜检查以确认Y染色体探针在肌成纤维细胞核内的位置。
发现纤维化区域中有大量Y染色体阳性细胞对α-SMA、波形蛋白和纤连蛋白-2呈阳性，而对CD45呈阴性，因此具有肌成纤维细胞表型。在肝移植病例中，6.8%-22.2%的α-SMA阳性肌成纤维细胞含有Y染色体。在接受男性供体骨髓移植的女性受者中，12.4%的肌成纤维细胞Y染色体呈阳性，表明起源于骨髓。
在多种病因的肝脏疾病中，肝外来源的肌成纤维细胞对人类肝硬化有显著贡献。
