PNAS:干细胞能存活多久?
患者在接收骨髓移植时,会接收一批新的造血干细胞。由于放疗或化疗治疗癌症,引起患者体内红细胞或白细胞数量偏低,贫血症患者将需要"新鲜"的干细胞。然而,移植的干细胞由于存活周期不长,或是干细胞增殖太旺盛以至于患上白血病,那么骨髓移植可能就不会成功。
为了确定骨髓(干细胞)移植持续的时间,桑德福伯纳姆医学院研究所的研究者开发了一个数学模型,预测干细胞的生存周期,并用小鼠模型做进一步测试。该项研究由斯塔姆勒教授主持,并发表在2月28日的《美国国家科学院院刊》(PNAS)上。
桑德福伯纳姆医学院主持干细胞与再生生物项目的斯塔姆勒教授说,长期以来一直认为干细胞是不会死亡的,他们持续自我更新,从而产生更多的干细胞。但是现在我们发现每个干细胞重组以进行自我更新只持续一段时间,小鼠试验表明从几个月到几年不等。所以我们创造了一个计算机程序以预测干细胞生命周期。研究者从移植接受者体内获取血液,对其产生的成熟白细胞进行初始测量,并将这些参数输入计算机程序中。这些信息与干细胞真正的生命周期做比较。一些干细胞可持续五个月,其他的可存活三年多,计算机程序总是以惊人的准确预测了干细胞的生命周期。
斯塔姆勒教授和她的同事们发现干细胞的自我更新是严格调控,从而达到一个不稳定的平衡,干细胞更新太过频繁导致白血病,太少的话骨髓移植失败。这一最新的认识使他们能更好地预测正常干细胞增殖的条件。
使用胚胎和其他干细胞进行组织再生的安全性和效率,将取决于准确控制干细胞增殖能力。通过更好地理解干细胞如何增殖,何时消亡,生命周期预测系统能进一步改善对于糖尿病、老年痴呆症和其他疾病的治疗。
英文链接:http://www.sciencedaily.com/releases/2011/03/110301111249.htm
中文链接: http://www.chinastemcell.org/page/zixun_xwdtlist.aspx?infoid=997
英文摘要:
PNAS February 28, 2011 DOI: 10.1073/pnas.1011414108
Predicting clonal self-renewal and extinction of hematopoietic stem cells.
Hans B. Sieburg, Betsy D. Rezner, and Christa E. Muller-Sieburg.
A single hematopoietic stem cell (HSC) can generate a clone, consisting of daughter HSCs and differentiated progeny, which can sustain the hematopoietic system of multiple hosts for a long time. At the same time, this massive expansion potential must be restrained to prevent abnormal, leukemic proliferation. We used an interdisciplinary approach, combining transplantation assays with mathematical and computational methods, to systematically analyze the proliferative potential of individual HSCs. We show that all HSC clones examined have an intrinsically limited life span. Daughter HSCs within a clone behaved synchronously in transplantation assays and eventually exhausted at the same time. These results indicate that each HSC is programmed to have a finite life span. This program and the memory of the life span of the mother HSC are inherited by all daughter HSCs. In contrast, there was extensive heterogeneity in life spans between individual HSC clones, ranging from 10 to almost 60 mo. We used model-based machine learning to develop a mathematical model that efficiently predicts the life spans of individual HSC clones on the basis of a few initial measurements of donor type cells in blood. Computer simulations predict that the probability of self-renewal decays with a logistic kinetic over the life span of a normal HSC clone. Other decay functions lead to either graft failure or leukemic proliferation. We propose that dynamical fate probabilities are a crucial condition that leads to self-limiting clonal proliferation.
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