Granulocyte Colony-Stimulating Factor Mobilizes Into Peripheral Blood the Complete Clonal Repertoire of Hematopoietic Precursors Residing in the Bone Marrow of Mice

Abstract

We have established the clonal relationships between the hematopoietic precursors residing in the bone marrow (BM) and the peripheral blood (PB) of mice treated with granulocyte colony-stimulating factor (G-CSF). The use of animals whose hematopoiesis was reconstituted with genetically labeled stem cells has allowed us to show that an almost identical repertoire of clones is found in the colony-forming unit (CFU-S) population present in the BM and mobilized PB. Moreover, our data has shown that the frequency of expression of the repopulating clones in both types of CFU-S populations is the same, evidencing that G-CSF mobilized PB progenitor cells (PBPCs) closely reflect the clonal make-up of the hematopoietic precursors residing in the BM. When secondary recipients were transplanted with BM or mobilized PB grafts that had been harvested from the genetically marked mice, the presence of long-term lympho-hematopoietic repopulating clones was showed not only in the BM but also in the PB samples. No new clones were identified in the long-term repopulating cells of the mobilized animals with respect to those found in the CFU-S population. Moreover, the hematopoietic precursors that were capable of long-term reconstitution corresponded to the clones, which were most highly represented in the CFU-S compartment, suggesting, at least in the case of G-CSF treated mice, that the frequency of expression of the repopulating clones in the CFU-S population is prognostic for the clone longevity. Based on our experimental data, new advantages for the use of mobilized PBPCs in place of hematopoietic grafts procured from limited areas of BM are proposed.