CD34+細(xì)胞：肝臟干細(xì)胞？造血干細(xì)胞？
本文由漢氏聯(lián)合專家團(tuán)隊(duì)翻譯
摘要：關(guān)于人類肝臟干/祖細(xì)胞的鑒定和起源由于缺少細(xì)胞發(fā)育潛能功能評(píng)估的小動(dòng)物模型而存在大量爭(zhēng)議。
近來有研究人員發(fā)現(xiàn)接受CD34+人胎肝細(xì)胞移植的亞致死劑量照射的NOD-SCID IL2rg-/-（NSG)小鼠，可以有效發(fā)育成人造血干細(xì)胞和人肝細(xì)胞樣細(xì)胞。利用這種簡(jiǎn)單的體內(nèi)分析方法和細(xì)胞分選，CD34+胎肝細(xì)胞可以分為三類不同的亞群：CD34hiCD133hi細(xì)胞群，CD34loCD133lo細(xì)胞群和CD34hiCD133neg細(xì)胞群。
CD34hiCD133hi細(xì)胞群含有造血干/祖細(xì)胞（HSPC），在體內(nèi)能夠產(chǎn)生T細(xì)胞，B細(xì)胞，NK細(xì)胞，樹突狀細(xì)胞，單核細(xì)/巨噬細(xì)胞，在體外生成CFU-GEMM。CD34loCD133lo細(xì)胞群不產(chǎn)生造血細(xì)胞，但是在體外及NSG小鼠體內(nèi)可重復(fù)產(chǎn)生肝細(xì)胞樣細(xì)胞。CD34hiCD133neg細(xì)胞群只能在體外生成CFU-GM和紅系爆發(fā)性形成單位（burst-forming unit-erythroid）。
進(jìn)一步研究表明，與成熟的肝臟細(xì)胞相比，CD34loCD133lo細(xì)胞群在表達(dá)和轉(zhuǎn)錄包括CD34、CD133、CD117、表皮細(xì)胞黏附分子、CD73、白蛋白、甲胎蛋白和波形蛋白在內(nèi)的造血、肝臟、間充質(zhì)干細(xì)胞的標(biāo)志方面更接近HSPC。這些結(jié)果提示CD34loCD133lo胎肝細(xì)胞具有肝臟祖細(xì)胞特點(diǎn)，說明盡管可能起源于胎兒肝臟的同一前體細(xì)胞群，肝臟祖細(xì)胞和造血祖細(xì)胞是明顯不同的。
原文地址：http://onlinelibrary.wiley.com/doi/10.1002/stem.1359/suppinfo
英文摘選：
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.
雜志：Stem Cells 2013;31:1160–1169
