Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells
Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells
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DOI：
10.1053/j.gastro.2005.10.049
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发表时间：
2006-02-01
期刊：
影响因子：
29.4
通讯作者：
Shafritz, DA
中科院分区：
文献类型：
--
作者：
Oertel, M;Menthena, A;Shafritz, DA
背景与目的：干细胞的一个关键特性是它们在非选择性条件下重建器官或组织的能力。本研究的目的是确定我们是否可以获得可重复的，高水平的肝再生移植胎肝干/祖细胞在正常成人肝脏和肝脏替代发生的机制。研究方法：野生型（二肽基肽酶IV [DPPIV+]）胚胎日（艾德）：将14个胎肝细胞移植到DPPIV突变型F344大鼠中，以跟踪移植细胞的命运和分化。为了确定再增殖的机制，还跟踪移植和宿主肝细胞的增殖和凋亡。结果如下：移植艾德14胎肝细胞持续增殖6个月，分化为成熟肝细胞，并取代总肝质量的23.5%。移植细胞的后代在形态上和功能上与宿主肝细胞没有区别，并表达与其在肝小叶中的位置相称的独特的肝脏特异性基因。再生是基于更大的增殖活性的移植细胞和减少凋亡的后代相比，宿主肝细胞，加上增加宿主肝细胞凋亡紧邻移植细胞。这个过程，被称为细胞间竞争，以前在果蝇翅膀发育过程中被描述过。结论：我们第一次表明，细胞间竞争，一个发展的范例，可以用来取代功能器官组织在一个成年哺乳动物物种的非选择性条件下，并可能作为一种策略，组织重建在各种各样的代谢和其他疾病，涉及肝脏，以及其他器官。
Background & Aims: A critical property of stem cells is their ability to repopulate an organ or tissue under nonselective conditions. The aims of this study were to determine whether we could obtain reproducible, high levels of liver repopulation by transplanted fetal liver stem/progenitor cells in normal adult liver and the mechanism by which liver replacement occurred. Methods: Wild-type (dipeptidyl peptidase IV [DPPIV+]) embryonic day (ED) :14 fetal liver cells underwent transplantation into DPPIV- mutant F344 rats to follow the fate and differentiation of transplanted cells. To determine the mechanism for repopulation, proliferation and apoptosis of transplanted and host liver cells were also followed. Results: Transplanted ED 14 fetal liver cells proliferated continuously for 6 months, differentiated into mature hepatocytes, and replaced 23.5% of total liver mass. The progeny of transplanted cells were morphologically and functionally indistinguishable from host hepatocytes and expressed unique liver-specific genes commensurate with their location in the hepatic lobule. Repopulation was based on greater proliferative activity of transplanted cells and reduced apoptosis of their progeny compared with host hepatocytes, coupled with increased apoptosis of host hepatocytes immediately adjacent to transplanted cells. This process, referred to as cell-cell competition, has been described previously in Drosophila during wing development. Conclusions: We show for the first time that cell-cell competition, a developmental paradigm, can be used to replace functional organ tissue in an adult mammalian species under nonselective conditions and may serve as a strategy for tissue reconstitution in a wide variety of metabolic and other disorders involving the liver, as well as other organs.