Immunohistochemical characterization of hepatic stem cell-related cells in developing human liver

Immunohistochemical characterization of hepatic stem cell-related cells in developing human liver
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人类肝脏发育过程中肝干细胞相关细胞的免疫组织化学特征

DOI:
10.1007/s11684-007-0050-2
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发表时间:
2007-07
期刊:
Frontiers of Medicine in China
影响因子:
--
通讯作者:
--
中科院分区:
其他
文献类型:
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不同发育阶段人胎肝中肝干细胞(hepatic stem cells,HSC)及其它HSC相关细胞的各种可能标志物的表达特征尚不清楚。研究肝星状细胞的免疫组化表达对了解肝星状细胞的起源、分化和迁移具有重要意义。应用HE染色和免疫组化方法,观察30例孕4-35周胎肝标本中肝/胆管细胞分化标志物(AFP、GST-π、CK 7、CK 19)和造血干细胞标志物(CD 34、c-kit)在几种HSC相关细胞中的表达。胎肝细胞在妊娠4周时出现AFP表达。它在妊娠16-24周达到高峰,之后逐渐减少。最后,仅在部分导管板细胞和少数界板细胞中发现弱信号。GST-π从第6周开始在肝索细胞中表达,从第8周开始在导管板细胞中表达。26周后,仅部分导管板细胞和少数界板细胞显示阳性信号。CK 19在第6 ~ 11周肝索细胞中表达最高,以后逐渐下降,除导管板外。14周开始,胆管板细胞和胆管细胞表达CK 7。第8周,在部分导管板细胞和汇管区肝索/间质组织中的少数单个核细胞中检测到CD 34和c-kit。21周后,CD 34和c-kit仅见于导管板细胞,汇管区间充质组织中有少量单个核细胞。胎龄4-16周的胎肝细胞主要由具有双潜能分化能力的HSC构成。孕16周时,大部分肝索细胞开始分化为肝细胞,肝管板(Hering管的起源部位)内仍有大量的HSC。研究还表明,胚胎肝脏中的造血干细胞可能具有部分造血干细胞的分化潜能。这间接支持了先前报道的肝谷假说中关于肝星状细胞的定位和起源的假说。
Little is known about the expression characteristics of the various kinds of possible markers in hepatic stem cells (HSCs) and other HSC-related cells in human fetal liver in various developmental stages. It is significant to investigate the immunohistochemical expression for better understanding of the origin, differentiation and migration of HSCs in the developing human liver. 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 HSC-related cells in thirty cases of fetal liver samples (4–35 weeks after pregnancy). AFP expression appears in fetal hepatocytes at four weeks’ gestation. It peaks at 16–24 weeks’ gestation and decreases 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 sixth week and in the ductal plate cells from the eighth week. Twenty-six weeks later, only some ductal plate cells and a few limiting plate cells show positive signals. CK19 expression peaks during the 6th–11th weeks in hepatic cord cells and decreases gradually afterwards, except for the ductal plates. CK7 expression was limited in the ductal plate cells and bile ducts cells from the 14th week. CD34 and c-kit were detected at the eighth week in some ductal plate cells and a few mononuclear cells in the hepatic cords/mesenchymal tissue of portal areas. 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. Fetal hepatocytes at 4–16 weeks’ gestation are mainly constituted by HSCs characterized with bi-potential differentiation capacity. At 16 weeks’ gestation, most hepatic cord cells begin to differentiate into hepatocytes and abundant HSCs remain in ductal plate (the origin site of Hering canals). It is also indicated that the hematopoietic stem cells may give rise to some HSCs in embryonic liver. These indirectly support the hypothesis about the location and origin of HSCs in “liver valley hypothesis” reported previously.
DOI: 10.1055/s-2004-815560
发表时间: 2003-11
影响因子: 4.2
作者:
M. Grompe
通讯作者: M. Grompe
DOI: 10.1053/jhep.2000.20349
发表时间: 2000-12-01
期刊: HEPATOLOGY
影响因子: 13.5
作者:
Suzuki, A;Zheng, YW;Taniguchi, H
通讯作者: Taniguchi, H
DOI: 10.1016/s0002-9440(10)65074-2
发表时间: 2000-06-01
影响因子: 6
作者:
Dabeva, MD;Petkov, PM;Shafritz, DA
通讯作者: Shafritz, DA
DOI: 10.1002/hep.510280412
发表时间: 1998-10-01
期刊: HEPATOLOGY
影响因子: 13.5
作者:
Crosby, HA;Hubscher, SG;Strain, AJ
通讯作者: Strain, AJ