Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal.

Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal.
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DOI:
10.1126/science.1256337
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发表时间:
2014-09-19
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Sauvageau G
Sauvageau G
中科院分区:
其他
文献类型:
--
作者:
Fares I;Chagraoui J;Gareau Y;Gingras S;Ruel R;Mayotte N;Csaszar E;Knapp DJ;Miller P;Ngom M;Imren S;Roy DC;Watts KL;Kiem HP;Herrington R;Iscove NN;Humphries RK;Eaves CJ;Cohen S;Marinier A;Zandstra PW;Sauvageau G

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脐带血单位中的造血干细胞和祖细胞数量少,限制了它们在人类移植方案中的广泛应用。我们发现了一个化学相关的小分子家族,可以刺激人类脐带血细胞的体外扩增,在免疫功能低下的小鼠中至少6个月的时间内重建人类造血功能。以UM171为原型,这些新发现的化合物的有效活性不依赖于对芳烃受体的抑制,而芳烃受体针对的是再生潜力有限的细胞。UM171的特性使其成为造血干细胞移植和基因治疗的潜在候选者。
The small number of hematopoietic stem and progenitor cells in cord blood units limits their widespread use in human transplant protocols. We identified a family of chemically related small molecules that stimulates the expansion ex vivo of human cord blood cells capable of reconstituting human hematopoiesis for at least 6 months in immunocompromised mice. The potent activity of these newly identified compounds, UM171 being the prototype, is independent of suppression of the aryl hydrocarbon receptor, which targets cells with more-limited regenerative potential. The properties of UM171 make it a potential candidate for hematopoietic stem cell transplantation and gene therapy.
DOI: 10.1016/j.stem.2007.05.015
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