The repopulation potential of hepatocyte populations differing in size and prior mitotic expansion
The repopulation potential of hepatocyte populations differing in size and prior mitotic expansion
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DOI：
10.1016/s0002-9440(10)65531-9
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发表时间：
1999-12-01
影响因子：
6
通讯作者：
Grompe, M
中科院分区：
文献类型：
--
作者：
Overturf, K;Al-Dhalimy, M;Grompe, M
最近，系列移植证实了成人肝细胞具有干细胞样再生潜能。这种再繁殖能力可能有助于通过细胞移植和/或扩增基因操纵的细胞来治疗遗传性肝病。然而，以前的实验使用的是未分离的肝细胞群，因此仍然不能确定是所有肝细胞还是只有一个亚群(干细胞)具有这种高再生能力。为了解决这个问题，我们使用离心洗脱来根据细胞密度分离肝细胞。出乎意料的是，小肝细胞(16微米)在第一轮移植中的再繁殖能力低于中等大小(21微米)和大细胞(27微米)。我们还比较了在体内经历了不同程度扩张的肝细胞的再繁殖能力。先前的细胞分裂既没有减少也没有增加移植肝细胞的再繁殖能力。最后，逆转录病毒标记实验证明，肝脏再生细胞的出现频率为1：10,000。我们的结论是，短期治疗性肝再生不需要祖细胞或干细胞。
Recently the stem cell-like regenerative potential of adult liver cells was demonstrated by serial transplantation. This repopulation capacity could be useful for the treatment of genetic liver diseases by cell transplantation and/or expansion of genetically manipulated cells. However, previous experiments used unfractionated populations of liver cells, and therefore it remained undetermined whether all hepatocytes or only a subpopulation (stem cells) possessed this high regenerative ability. To address this question we used centrifugal elutriation to separate hepatocytes by cell density. Unexpectedly, small hepatocytes (16 mu m) had lower repopulation capacity during the first round of transplantation when compared with both the medium-sized (21 mu m) and large (27 mu m) cells. We also compared the repopulation capacity of hepatocytes that had undergone different degrees of in vivo expansion. Previous cell division neither reduced nor increased the repopulation capacity of transplanted liver cells. Finally, retroviral tagging experiments demonstrated that liver-repopulating cells occur at a frequency of >1:10,000. We conclude that short-term therapeutic liver repopulation does not require progenitor or stem cells.