Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization
Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization
复制标题
DOI：
10.1073/pnas.94.5.1908
复制
发表时间：
1997-03-04
影响因子：
11.1
通讯作者：
Weissman, IL
中科院分区：
文献类型：
--
作者：
Morrison, SJ;Wright, DE;Weissman, IL
我们从用环磷酰胺（CY）和粒细胞集落刺激因子（G-CSF）处理的小鼠中分离造血干细胞（HSC），所有动员的多能祖细胞活性包含在两个群体中：Thy-1（lo）Sca-1（+）Lin（-）Mac-1（-）CD4（-）c-kit（+）长期重建祖细胞和Thy-1（lo）Sca-1（+）Lin（-）Mac-1（lo）CD4（-）瞬时重建祖细胞，CY/G-CSF治疗驱使长期和短暂的多能祖细胞进入周期，导致动员前长期自我更新的HSC数量增加12倍以上。CY和G-CSF治疗2天后，骨髓HSC数量开始下降，血液和脾脏HSC数量增加。经G-CSF处理8天后，HSC在骨髓和脾脏中继续增殖，但释放到血液中的HSC趋向于G（0）/G（1）期，从脾分离的动员多能祖细胞在移植辐射小鼠中的效率低于正常骨髓多能祖细胞，但在脾集落形成单位（CFU-S）中没有差异。这些数据表明，从脾分离的动员的HSC在归巢和移植到辐射受体小鼠的骨髓中的效率较低。
We isolated hematopoietic stem cells (HSC) from mice treated with cyclophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF), All mobilized multipotent progenitor activity was contained in two populations: Thy-1(lo)Sca-1(+)Lin(-)Mac-1(-)CD4(-)c-kit(+) long-term reconstituting progenitors and Thy-1(lo)Sca-1(+)Lin(-)Mac-1(lo)CD4(-) transiently reconstituting progenitors, CY/G-CSF treatment drove both long-term and transient multipotent progenitors into cycle, leading to a more than 12-fold expansion in the number of long-term self-renewing HSC prior to mobilization. After CY and 2 days of G-CSF treatment the number of bone marrow HSC began to decline and the number of blood and splenic HSC increased. HSC continued to proliferate in the bone marrow and spleen through 8 days of G-CSF treatment, but HSC released into the blood tended to be in G(0)/G(1) phase, Mobilized multipotent progenitors isolated from the spleen were less efficient than normal bone marrow multipotent progenitors in engrafting irradiated mice but did not differ in colony forming unit-spleen (CFU-S) activity or single cell in vitro assays of primitive progenitor activity, The data suggest that mobilized HSC isolated from the spleen are less efficient at homing to and engrafting the bone marrow of irradiated recipient mice.