| 摘要: |
| 目的：观察人胚胎发育不同时期胚胎肝组织中细胞免疫表型及其变化，探讨人肝干细胞的来源、分化与迁移规律。方法：用常规病理H—E染色和免疫组织化学方法观察30例4～35周龄胚胎肝组织中几种细胞的肝胆标记（AFP、GST-π、CK7、CK19）和造血干细胞标记（CD34、c-kit）的表达及变化。结果：AFP阳性表达始于4周龄胚胎肝，至16～24周龄达到高峰，之后表达逐渐减少，仅部分胆管板和少数界板细胞阳性；GST-π阳性表达始于6周龄后的胚胎肝肝索细胞和8周龄后胆管板细胞，但26周龄后仅部分胆管板细胞及少数界板细胞阳性。CK19在6～11周龄肝索细胞内阳性表达达到最高峰，之后表达逐渐减少但胆管板细胞始终阳性；CK7仅限于14周龄之后的胆管板细胞和胆管上皮内表达。8周龄胚胎肝胆管板中开始可见CD34和c-kit阳性细胞，肝索和门静脉附近间充质内也可见少数表达CD34和c-kit的单个核细胞；但21周龄后CD34和c-kit阳性细胞仅见于胆管板及汇管区间充质内而肝索内少见。结论：4～16周龄胚胎肝细胞主要由具有双向分化潜能的肝干细胞组成；16周龄胚胎肝内大部分肝索细胞开始表现出向肝细胞定向分化的特点，而作为未来Hering管细胞来源的胆管板则仍含有肝干细胞；胚胎肝内部分肝干细胞可能来源于造血系统；这些与前期研究提出的“肝流域假设”中涉及肝干细胞所在及来源的假设相吻合 |
| 关键词: 胚胎 肝干细胞 免疫组织化学 肝流域假设 |
| DOI：10.3724/SP.J.1008.2007.00117 |
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| 基金项目:国家自然科学基金(30570836);; 中国人民解放军第105医院科研基金(2006004-A). |
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| Immunohistochemical characterization of hepatic stem cells in developing human liver |
| XU Jun1; HU Yong1; WANG Jian1; ZHOU Ji2; ZHANG Tai-ping1; YU Hong-yu3* |
| (1.Department of Pathology; No. 105 Hospital of PLA; Hefei 230031; China; 2.Department of Obstetrics and Gynecology; Second People’s Hospital of Yaohai District; Hefei 230011; 3. Department of Pathology; Changzheng Hospital; Second Military Medical University; Shanghai 200003) |
| Abstract: |
| Objective：To investigate the immunohistochemical characterization of hepatic stem cells in the developing human liver, so as to study the origin, differentiation and migration of hepatic stem cells. Methods： H-E staining and immunohistochemical methods were used to observe the expression of hepatic/cholangiocellular differentiation markers （ AFP, GST-π, CK7, CK19 ） and hematopoietic stem cell markers （CD34 and c-kit） in several kinds of cells obtained from thirty 4- to 35-week old fetal liver samples. Results： AFP expression appeared in fetal liver at 4 weeks＇ gestation, peaked during 16-24 weeks＇ gestation and decreased gradually afterwards; finally weak signals were only found in some ductal plate cells and a few limiting plate cells. GST-π was detected in hepatic cord cells from the 6^th week and in the ductal plate cells from the 8^th week; 26 weeks later, only some ductal plate cells and a few limiting plate cells showed positive signals. CK19 expression peaked during 6^th to 11^th week in hepatic cord cells and decreased gradually afterwards, except for that in the ductal plates. CK7 expression was limited in the ductal plate cells and bile duct cells from the 14^th week. CD34 and c-kit were detected at the 8^th week in some ductal plate cells and a few mononuclear cells in the hepatic cords/mesenchymal tissue of portal area; after 21 weeks, CD34 and c-kit were found only in ductal plate cells and a few mononuclear cells in the hepatic mesenchymal tissue of portal areas. Conclusion; Fetal hepatocytes at 4-16 weeks＇ gestation are mainly constituted by hepatic stem cells with bi-potential differentiation capacity. At 16 weeks＇ gestation, most hepatic cord cells begin to differentiate into hepatocytes and abundant hepatic stem cells remain in the ductal plate （ the origin site of Hering canals）. It is also indicated that the hematopoietic stem cells may give rise to some hepatic stem cells in embryonic liver. These indirectly support the hypothesis about the location and origin of liver stem cells in ＂liver valley hypothesis＂ reported previously. |
| Key words: embryo hepatic stem cells immunohistochemistry liver valley hypothesis |
