Combination of rhSCF + rhG-SCF, But Not rhG-CSF Alone Potentiate the Mobilization of Hematopoietic Stem Cells with Increased Repopulating Ability into Peripheral Blood of Mice

Abstract

The early hematopoietic progenitor including cells capable for long-term maintenance of hematopoiesis circulates in low amount in peripheral blood during steady-state conditions [1–4]. However, these progenitors were found to belong to one of more mature category in the hierarchy of hematopoietic stem cells (HSC). Indeed, in competitive repopulation assays the progeny of peripheral blood HSC is rapidly replaced by the progeny of bone marrow stem cells [5,6]. During last decade it was repeatedly demonstrated that some hematopoietic cytokines affect not only survival, proliferation and differentiation of hematopoietic cells, but also capable to mobilize HSC into circulation [7–11]. Such ability of cytokines is studying very intensively both in experimental and clinical conditions because mobilized HSC can be used itself or in combination with bone marrow cells as a source of progenitors for transplantation [12]. Among cytokines capable to mobilize HSC into circulation the most attention are payed now on SCF and its combination with other growth factors, especially G-CSF [7,13,14]. Inspite of the cytokine-mobilized HSC (usually after intensive course of chemotherapy in the period of regeneration of hematopoiesis) are now used in patients, a lot of questions has no answer. Up to now it is obscure if peripheral blood progenitors are mobilized from bone marrow by pharmacological doses of cytokines or their expansion in bone marrow and/or peripheral blood take place. For G-CSF it was shown that more probable mechanism is HSC mobilization [7,15]. The data about similar effect of G-CSF plus SCF combination was not published; meanwhile, SCF in combination with other cytokines produces in vitro more strong effect on HSC proliferation than G-CSF alone [14,16]. We have no data about the optimal time of peripheral blood HSC (pbHSC) collection: is it necessary to collect pbHSC during their highest concentration or later in the cytokine course when pbHSC level is not so high, but quality of progenitors possibly better, for example because of enrichment of population by more immature members of HSC compartment? Here these questions were addressed on murine system with use of rhG-CSF and rhSCF.