CD34+细胞：肝脏干细胞？造血干细胞？
本文由汉氏联合专家团队翻译
摘要：关于人类肝脏干/祖细胞的鉴定和起源由于缺少细胞发育潜能功能评估的小动物模型而存在大量争议。
近来有研究人员发现接受CD34+人胎肝细胞移植的亚致死剂量照射的NOD-SCID IL2rg-/-（NSG)小鼠，可以有效发育成人造血干细胞和人肝细胞样细胞。利用这种简单的体内分析方法和细胞分选，CD34+胎肝细胞可以分为三类不同的亚群：CD34hiCD133hi细胞群，CD34loCD133lo细胞群和CD34hiCD133neg细胞群。
CD34hiCD133hi细胞群含有造血干/祖细胞（HSPC），在体内能够产生T细胞，B细胞，NK细胞，树突状细胞，单核细/巨噬细胞，在体外生成CFU-GEMM。CD34loCD133lo细胞群不产生造血细胞，但是在体外及NSG小鼠体内可重复产生肝细胞样细胞。CD34hiCD133neg细胞群只能在体外生成CFU-GM和红系爆发性形成单位（burst-forming unit-erythroid）。
进一步研究表明，与成熟的肝脏细胞相比，CD34loCD133lo细胞群在表达和转录包括CD34、CD133、CD117、表皮细胞黏附分子、CD73、白蛋白、甲胎蛋白和波形蛋白在内的造血、肝脏、间充质干细胞的标志方面更接近HSPC。这些结果提示CD34loCD133lo胎肝细胞具有肝脏祖细胞特点，说明尽管可能起源于胎儿肝脏的同一前体细胞群，肝脏祖细胞和造血祖细胞是明显不同的。
原文地址：http://onlinelibrary.wiley.com/doi/10.1002/stem.1359/suppinfo
英文摘选：
Human Fetal Hepatic Progenitor Cells Are Distinct from, but Closely Related to, Hematopoietic Stem/Progenitor Cells
Much controversy surrounds the identity and origin of human hepatic stem and progenitor cells in part because of a lack of small animal models in which the developmental potential of isolated candidate cell populations can be functionally evaluated. We show here that adoptive transfer of CD34+ cells from human fetal liver into sublethally irradiated NOD-SCID Il2rg−/− (NSG) mice leads to an efficient development of not only human hematopoietic cells but also human hepatocyte-like cells in the liver of the recipient mice. Using this simple in vivo assay in combination with cell fractionation, we show that CD34+ fetal liver cells can be separated into three distinct subpopulations: CD34hiCD133hi, CD34loCD133lo, and CD34hiCD133neg. The CD34hiCD133hi population contains hematopoietic stem/progenitor cells (HSPCs) as they give rise to T cells, B cells, NK cells, dendritic cells, and monocytes/macrophages in NSG mice and colony-forming unit (CFU)-GEMM cells in vitro. The CD34loCD133lo population does not give rise to hematopoietic cells, but reproducibly generates hepatocyte-like cells in NSG mice and in vitro. The CD34hiCD133neg population only gives rise to CFU-GM and burst-forming unit-erythroid in vitro. Furthermore, we show that the CD34loCD133lo cells express hematopoietic, hepatic, and mesenchymal markers, including CD34, CD133, CD117, epithelial cell adhesion molecule, CD73, albumin, α-fetal protein, and vimentin and transcriptionally are more closely related to HSPCs than to mature hepatocytes. These results show that CD34loCD133lo fetal liver cells possess the hepatic progenitor cell properties and that human hepatic and hematopoietic progenitor cells are distinct, although they may originate from the same precursors in the fetal liver.
杂志：Stem Cells 2013;31:1160–1169
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