Human hepatic progenitor cells express hematopoietic cell markers CD45 and CD109.

Human hepatic progenitor cells express hematopoietic cell markers CD45 and CD109.
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DOI:
10.7150/ijms.7426
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发表时间:
2014
影响因子:
3.6
通讯作者:
Li L
Li L
中科院分区:
医学4区
文献类型:
--
作者:
Li J;Xin J;Zhang L;Wu J;Jiang L;Zhou Q;Li J;Guo J;Cao H;Li L

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目的:明确人肝祖细胞(HPCs)的特性,为肝脏疾病的细胞治疗奠定基础。研究方法:肝祖细胞样细胞是从因各种病理而接受部分肝切除术但未显示肝功能障碍迹象的患者的肝脏中分离和培养的。这些细胞的特点是转录组学分析,定量实时PCR和免疫细胞/组织化学。结果:培养的HPCs呈多边形,核质比高,基因表达谱与原代肝细胞相似(67.8%)。在HPC中表达高20倍以上的基因包括祖细胞标志物(CD 90)、五聚蛋白相关基因(PTX 3)、胶原蛋白(COL 5A 2、COL 1A 1和COL 4A 2)、细胞因子(EGF和PDGFD)、代谢酶(CYBRD 1、BCAT 1、TIMP 2和PAM)、分泌蛋白(CYP)和内皮蛋白C受体(PROCR)。此外,通过qRT-PCR和/或免疫细胞/组织化学验证了先前描述为HPC标志物的8种标志物(ALB、AFP、CK 8、CK 18、CK 19、CD 90、CD 117和Oval-6)。有趣的是,人HPC也对造血细胞标志物CD 45和CD 109呈阳性。最后,我们的特点定位的HPC在运河的Hering和门静脉周围地区与六个以前描述的标志物(椭圆形-6,CK 8,CK 18,CK 19,CD 90和CD 117)和两个潜在的标志物(CD 45和CD 109)。结论:人HPCs与原代肝细胞在转录水平上高度相似。CD 45和CD 109标记物可能用于识别和分离HPC,用于进一步的肝脏疾病的细胞治疗。
Objective: To clarify the precise characteristics of human hepatic progenitor cells (HPCs) for future cytotherapy in liver diseases. Methods: Hepatic progenitor-like cells were isolated and cultured from the livers of patients who had undergone partial hepatectomy for various pathologies but displayed no sign of hepatic dysfunction. These cells were characterized by transcriptomic profiling, quantitative real-time PCR and immunocyto/histochemistry. Results:Cultured HPCs contained polygonal, high nucleus/cytoplasm ratio and exhibited a global gene expression profile similar (67.8%) to that of primary hepatocytes. Among the genes with more than 20-fold higher expression in HPCs were a progenitor marker (CD90), a pentraxin-related gene (PTX3), collagen proteins (COL5A2, COL1A1 and COL4A2), cytokines (EGF and PDGFD), metabolic enzymes (CYBRD1, BCAT1, TIMP2 and PAM), a secreted protein (SPARC) and an endothelial protein C receptor (PROCR). Moreover, eight markers (ALB, AFP, CK8, CK18, CK19, CD90, CD117 and Oval-6) previously described as HPC markers were validated by qRT-PCR and/or immunocyto/histochemistry. Interestingly, human HPCs were also positive for the hematopoietic cell markers CD45 and CD109. Finally, we characterized the localization of HPCs in the canals of Hering and periportal areas with six previously described markers (Oval-6, CK8, CK18, CK19, CD90 and CD117) and two potential markers (CD45 and CD109). Conclusion: The human HPCs are highly similar to primary hepatocytes in their transcriptional profiles. The CD45 and CD109 markers could potentially be utilized to identify and isolate HPCs for further cytotherapy of liver diseases.
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发表时间: 2006-05-01
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