Department of Hepatobiliary Surgery and Transplant Surgery, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
World J Gastroenterol. 2010 Jan 14;16(2):217-24. doi: 10.3748/wjg.v16.i2.217.
To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells.
Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry. Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1 (SDF-1) were measured using an enzyme linked immunosorbent assay.
Progenitor cells with a CD133(+)/CD45(+)/CD14(+) phenotype were observed in 61% of the patients. Between 1% and 26% of the peripheral blood mononuclear cells (MNCs) displayed this phenotype. Furthermore, a distinct population of c-kit(+) progenitor cells (between 1% and 38% of the MNCs) could be detected in 91% of the patients. Additionally, 18% of the patients showed a population of progenitor cells (between 1% and 68% of the MNCs) that was characterized by expression of breast cancer resistance protein-1. Further phenotypic analysis disclosed that the circulating precursors expressed CXC chemokine receptor 4, the receptor for SDF-1. In line with this finding, elevated plasma levels of SDF-1 were present in all patients and were found to correlate with the number of mobilized CD133(+) progenitor cells.
These data indicate that in humans, liver cirrhosis leads to recruitment of various populations of hematopoietic progenitor cells that display markers of intrahepatic progenitor cells.
验证肝硬化与造血祖细胞动员有关的假说。
通过流式细胞术分析了 72 例不同病因的肝硬化患者的外周血样本。免疫选择鉴定的祖细胞亚群，并用于体外功能测定。使用酶联免疫吸附试验测量基质细胞衍生因子-1（SDF-1）的血浆水平。
在 61%的患者中观察到具有 CD133(+)/CD45(+)/CD14(+)表型的祖细胞。1%至 26%的外周血单核细胞（MNC）显示出这种表型。此外，在 91%的患者中可以检测到明显的 c-kit(+)祖细胞群（占 MNC 的 1%至 38%）。此外，18%的患者表现出祖细胞群（占 MNC 的 1%至 68%），其特征是表达乳腺癌耐药蛋白-1。进一步的表型分析显示，循环前体细胞表达 CXC 趋化因子受体 4，这是 SDF-1 的受体。与这一发现一致，所有患者的 SDF-1 血浆水平升高，并与动员的 CD133(+)祖细胞数量相关。
这些数据表明，在人类中，肝硬化导致各种造血祖细胞群的募集，这些祖细胞群显示出肝内祖细胞的标志物。
