In vivo kinetics of murine hemopoietic stem cells
In vivo kinetics of murine hemopoietic stem cells
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DOI：
10.1182/blood.v96.10.3399.h8003399_3399_3405
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发表时间：
2000-11-15
期刊：
影响因子：
20.3
通讯作者：
Guttorp, P
中科院分区：
文献类型：
--
作者：
Abkowitz, JL;Golinelli, D;Guttorp, P
我们使用随机模型和计算机模拟来研究小鼠造血干细胞（hsc）在体内的复制、凋亡和分化，这种方法可以根据观察到的后代细胞（粒细胞和淋巴细胞）的行为来描述未观察到的群体（hsc）的行为。先前在44只小鼠中进行的限制稀释、竞争再种群研究的结果与模拟移植研究的结果进行了比较，以确定导致可比结果的参数。使用这种方法，我们估计小鼠造血干细胞每2.5周复制（平均）一次，并且小鼠造血干细胞的频率为每10(5)个有核骨髓细胞中有8个。如果假设短期再生细胞与造血干细胞不同，它们有助于移植后早期的造血，并且它们是独立调节的，那么每105个有核骨髓细胞中4个造血干细胞的频率也允许模拟最接近观察到的数据。当随机建模和计算机模拟应用于限制稀释，自体移植研究猫杂合葡萄糖-6-磷酸脱氢酶，不同的估计HSC复制率（1每8.3-10周）和频率（6每10(7)个细胞）得到。因此，这些参数似乎与寿命、尺寸或两者的增加成反比。这些数据的一个暗示是，人类造血干细胞的频率可能更低，复制更慢。这些关于细胞动力学的发现有几个含义。(C) 2000年由美国血液学会出版。
We used stochastic modeling and computer simulation to study the replication, apoptosis, and differentiation of murine hemopoietic stem cells (HSCs) in vivo, This approach allows description of the behavior of an unobserved population tie, HSCs) on the basis of the behavior of observed progeny cells tie, granulocytes and lymphocytes). The results of previous limiting-dilution, competitive-repopulation studies in 44 mice were compared with the results of simulated transplantation studies to identify parameters that led to comparable outcomes. Using this approach, we estimated that murine HSCs replicate ton average) once every 2.5 weeks and that the frequency of murine HSCs is 8 per 10(5) nucleated marrow cells. If it is assumed that short-term repopulating cells are distinct from HSCs, that they contribute to hemopoiesis early after transplantation, and that they are independently regulated, a frequency of 4 HSCs per 105 nucleated marrow cells also allows simulations that best approximate the observed data. When stochastic modeling and computer simulation were applied to limiting-dilution, autologous-transplantation studies in cats heterozygous for glucose-6-phosphate-dehydrogenase, different estimates of HSC replication rate (1 per 8.3-10 weeks) and frequency (6 per 10(7) cells) were derived. Therefore, it appears that these parameters vary inversely with increased longevity, size, or both. An implication of these data is that human HSCs may be less frequent and replicate more slowly. These findings on cell kinetics have several implications. (C) 2000 by The American Society of Hematology.