Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium
Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium
复制标题
DOI：
10.1053/gast.2001.21175
复制
发表时间：
2001-02-01
期刊：
影响因子：
29.4
通讯作者：
Strain, AJ
中科院分区：
文献类型：
--
作者：
Crosby, HA;Kelly, DA;Strain, AJ
背景与目的：最近的报道表明，骨髓移植到啮齿类动物和人类体内后，造血干细胞迁移到肝脏，形成卵圆细胞、肝细胞和胆管上皮细胞。我们在人体肝脏中使用造血标记物c-kit和CD34进一步研究了这一假说。方法：用细胞角蛋白19(CK-19；胆汁细胞标记物)和c-kit或CD34进行免疫荧光共聚焦显微镜检查。然后使用免疫磁分离来选择c-Hit或CD34阳性细胞。贴壁后培养7d，观察细胞生长情况和表型特征。结果：在肝硬变组织中，c-kit或CD34阳性细胞位于胆管周围的门管区。偶见共表达CK-19的c-kit-(但不是CD34-)阳性细胞整合到胆管中。在体外，免疫分离的c-kit或CD34细胞可产生至少两种形态的克隆，表达CK-19或CD31(内皮细胞标志)。具有相似特性的CD34或c-Hit阳性细胞也从正常肝脏中分离出来。结论：人类肝脏中表达c-kit或CD34标志物的细胞具有分化为胆管上皮细胞系的能力，因此可能代表人胆管上皮祖细胞。
Background & Aims: Recent reports suggest that after bone marrow transplantation into rodents and humans, hematopoietic stem cells migrate into the liver and give rise to oval cells, hepatocytes, and biliary epithelial cells. We investigated this hypothesis further in the human liver using the hematopoietic markers c-kit and CD34. Methods: Immunofluorescence confocal microscopy was performed using cytokeratin 19 (CK-19; biliary cell marker) with either c-kit or CD34. Immunomagnetic separation was then used to select c-hit- or CD34-positive cells. After attachment, cells were cultured for up to 7 days, and their growth and phenotypic characteristics were examined. Results: In cirrhotic tissue, c-kit- or CD34-positive cells were located in the portal tracts surrounding bile ducts. Occasionally c-kit- (but not CD34-) positive cells that coexpressed CK-19 were observed integrated into bile ducts. In vitro, immunoisolated c-kit or CD34 cells gave rise to colonies of at least 2 morphologies expressing CK-19 or CD31 (endothelial cell marker). CD34- or c-hit-positive cells with similar properties were also isolated from normal liver. Conclusions: These findings indicate that cells present in human liver that express the markers c-kit or CD34 have the capacity to differentiate into biliary epithelial cell lineage and may therefore represent human biliary epithelial progenitor cells.