Peripheral blood progenitor cell mobilisation alters myeloid, but not erythroid, progenitor cell self-renewal kinetics.
Transplantation of progenitor cells which have been mobilised into the bloodstream (PBPC) following the administration of G-CSF results in more rapid neutrophil recovery than transplantation of bone marrow (BM). The reasons for the accelerated neutrophil engraftment are not clear, but would be explained by increased self-replication of myeloid progenitor cells (CFU-GM). We have used a CFU-GM replating assay to investigate myeloid progenitor self-replication, and quantification of subcolony formation during erythroid burst formation to quantify erythroid progenitor self-renewal. Secondary colony formation by CFU-GM, grown from PBPC and then replated was increased compared with secondary colony formation by BM CFU-GM (P = 0.0001); erythroid subcolony formation was not altered. There was no difference between the replating abilities of PBPC CFU-GM derived from allogeneic donors (normal individuals) and autologous donors (patients with malignant disease) although differences were found between subgroups of autologous donors. The increased replication of PBPC could not be accounted for by a reduction in progenitor cell apoptosis; PBPC CFU-GM contained slightly fewer apoptotic CD34+ cells than BM CFU-GM. The increased replication by PBPC CFU-GM was reversible because it declined when CFU-GM colonies were passaged through three sequential CFU-GM replating cycles. This decline in self-replication was more rapid than the decline seen in replated BM CFU-GM. The self-replication of PBPC CFU-GM, and subcolony formation by BFU-E could be further enhanced by exposure to cytokines in vitro. We conclude that mobilisation alters the replication kinetics of myeloid, but not of erythroid, progenitor cells, that mobilisation-induced events are of limited duration and that in vitro exposure to cytokines may modify PBPC progenitor cell kinetics.
Leukaemia Research Fund Centre for Adult Leukaemia , Department of Hematology, Imperial College School of Medicine, London, UK.
S B
SB
Marley
J L
JL
Lewis
B
B
Zheng
R J
RJ
Davidson
J G
JG
Davis
C
C
McDonald
F Q
FQ
Alenzi
J M
JM
Goldman
M Y
MY
Gordon
D001773:Blood Cells / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D019337:Hematologic Neoplasms / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007700:Kinetics; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects*
D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor