Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization

SJ Morrison, DE Wright… - Proceedings of the …, 1997 - National Acad Sciences
SJ Morrison, DE Wright, IL Weissman
Proceedings of the National Academy of Sciences, 1997National Acad Sciences
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-1loSca-1+ Lin− Mac-1− CD4− c-kit+ long-term
reconstituting progenitors and Thy-1loSca-1+ Lin− Mac-1loCD4− 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 …
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-1loSca-1+LinMac-1CD4c-kit+ long-term reconstituting progenitors and Thy-1loSca-1+LinMac-1loCD4 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 G0/G1 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.
National Acad Sciences