患者在接收骨髓移植時,,會接收一批新的造血干細(xì)胞,。由于放療或化療治療癌癥,引起患者體內(nèi)紅細(xì)胞或白細(xì)胞數(shù)量偏低,,貧血癥患者將需要"新鮮"的干細(xì)胞,。然而,移植的干細(xì)胞由于存活周期不長,,或是干細(xì)胞增殖太旺盛以至于患上白血病,,那么骨髓移植可能就不會成功。
為了確定骨髓(干細(xì)胞)移植持續(xù)的時間,,桑德福伯納姆醫(yī)學(xué)院研究所的研究者開發(fā)了一個數(shù)學(xué)模型,,預(yù)測干細(xì)胞的生存周期,并用小鼠模型做進(jìn)一步測試,。該項研究由斯塔姆勒教授主持,,并發(fā)表在2月28日的《美國國家科學(xué)院院刊》(PNAS)上。
桑德福伯納姆醫(yī)學(xué)院主持干細(xì)胞與再生生物項目的斯塔姆勒教授說,,長期以來一直認(rèn)為干細(xì)胞是不會死亡的,,他們持續(xù)自我更新,從而產(chǎn)生更多的干細(xì)胞,。但是現(xiàn)在我們發(fā)現(xiàn)每個干細(xì)胞重組以進(jìn)行自我更新只持續(xù)一段時間,,小鼠試驗表明從幾個月到幾年不等。所以我們創(chuàng)造了一個計算機程序以預(yù)測干細(xì)胞生命周期,。研究者從移植接受者體內(nèi)獲取血液,,對其產(chǎn)生的成熟白細(xì)胞進(jìn)行初始測量,并將這些參數(shù)輸入計算機程序中,。這些信息與干細(xì)胞真正的生命周期做比較,。一些干細(xì)胞可持續(xù)五個月,其他的可存活三年多,,計算機程序總是以驚人的準(zhǔn)確預(yù)測了干細(xì)胞的生命周期,。
斯塔姆勒教授和她的同事們發(fā)現(xiàn)干細(xì)胞的自我更新是嚴(yán)格調(diào)控,從而達(dá)到一個不穩(wěn)定的平衡,,干細(xì)胞更新太過頻繁導(dǎo)致白血病,,太少的話骨髓移植失敗。這一最新的認(rèn)識使他們能更好地預(yù)測正常干細(xì)胞增殖的條件,。
使用胚胎和其他干細(xì)胞進(jìn)行組織再生的安全性和效率,,將取決于準(zhǔn)確控制干細(xì)胞增殖能力。通過更好地理解干細(xì)胞如何增殖,,何時消亡,,生命周期預(yù)測系統(tǒng)能進(jìn)一步改善對于糖尿病、老年癡呆癥和其他疾病的治療,。(生物谷Bioon.com)
英文鏈接:http://www.sciencedaily.com/releases/2011/03/110301111249.htm
中文鏈接: http://www.chinastemcell.org/page/zixun_xwdtlist.aspx?infoid=997
生物谷推薦英文摘要:
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.