scholarly journals Individual Differences in the Radiosensitivity of Hematopoietic Progenitor Cells Detected in Steady-State Human Peripheral Blood

2008 ◽  
Vol 49 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Asami ORIYA ◽  
Kenji TAKAHASHI ◽  
Osamu INANAMI ◽  
Toshiaki MIURA ◽  
Yoshinao ABE ◽  
...  
Keyword(s):  
Steady State ◽  
Individual Differences ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor

scholarly journals Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy [see comments]

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2619-2626 ◽  
Author(s):  
S Fruehauf ◽  
R Haas ◽  
C Conradt ◽  
S Murea ◽  
B Witt ◽  
...  
Keyword(s):  
Steady State ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Cytotoxic Chemotherapy ◽  
Hematopoietic Progenitor Cells ◽  
Low Grade ◽  
Hematopoietic Progenitor ◽  
Cd34 Antigen ◽  
Cd34 Cells

Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic chemotherapy and cytokines. There is a substantial variability in the yield of hematopoietic progenitor cells between patients. We were looking for predictive parameters indicating a patient's response to a given mobilization regimen. Multiparameter flow-cytometry analysis and clonogenic assays were used to examine the hematopoietic progenitor cells in bone marrow (BM) and peripheral blood (PB) before filgrastim (R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in PB and leukapheresis products (LPs) in the recovery phase. Fifteen patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence plots showed a homogenous population of strongly CD34+ cells in steady-state and mobilized PB whereas in steady-state BM, the CD34+ cells ranged from strongly positive with continuous transition to the CD34- population. Consistent with the similarity in CD34 antigen expression, a correlation analysis showed steady-state PB CD34+ cells (r = .81, P < .001) and colony-forming cells (CFCs; r = .69, P < .01) to be a measure of a patient's mobilizable CD34+ cell pool. Individual estimates of progenitor cell yields could be calculated. With a probability of 95%, eg, 0.4 steady-state PB CD34+ cells x 10(6)/L allowed to collect in six LPs 2.5 x 10(6) CD34+ cells/kg, the reported threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR-subset nor the BM CFC count had a predictive value for the mobilization outcome. This may be caused by the additional presence of maturing progenitor cells in BM, which express lower levels of the CD34 antigen and do not circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.

AMD3100 Signals Via the Nervous System, Inducing Release to the Circulation of Bone Marrow SDF-1, Which Is Crucial for Progenitor Cell Mobilization.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1315-1315 ◽  
Author(s):  
Ayelet Dar ◽  
Alexander Kalinkovich ◽  
Neta Netzer ◽  
Raanan Margalit ◽  
Amir Schajnovitz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Nervous System ◽  
Steady State ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Neutralizing Antibodies ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor

Abstract AMD3100, a bicyclam antagonist of the chemokine receptor CXCR4 in vitro, has been shown to induce rapid mobilization of human and murine maturing leukocytes and immature hematopoietic stem and progenitor cells in vivo. In addition, AMD3100 combined with G-CSF, synergistically augments mobilization of human progenitor cells (Broxmeyer & Srour et al, JEM, 2005). However, the mechanism of AMD3100-induced mobilization is currently poorly understood. We report that AMD3100-induced mobilization in mice was accompanied with rapid increase in functional SDF-1 concentrations in the circulation and their parallel decrease in the bone marrow within 1 hour. Biotinylated SDF-1 (bSDF-1) directly injected into the femur was detected in the peripheral blood, adjacent bones and spleen as early as 10 minutes post administration. Interestingly, AMD3100 induced significant elevations in bone marrow-derived bSDF-1 concentrations in the peripheral blood. Similarly, G-CSF induced mobilization was initiated (24 hours post a single injection of G-CSF), by SDF-1 release to the circulation. Administration of neutralizing antibodies against CXCR4 to either untreated or AMD3100 treated mice markedly reduced SDF-1 levels in the peripheral blood, coinciding with increased retention levels of this ligand in the bone marrow. In vitro, AMD3100 directly induced SDF-1 release from the human osteoblast cell line MG-63 in a bell shaped dose response. Inhibition of CXCR4-dependent release of SDF-1 during homeostasis or upon treatment with AMD3100, correlated with selective reduction in recruitment of hematopoietic progenitor cells but not mature leukocytes to the circulation. Importantly, injection of neutralizing antibodies against SDF-1 (but not matched control antibodies) resulted in decreased steady state egress and AMD3100-induced mobilization of hematopoietic progenitor cells. Rapid recruitment (within 1 hour) of hematopoietic progenitor cells and maturing leukocytes out of the bone marrow as well as SDF-1 release were dependent on signals from the nervous system. Administration of the b2 adrenergic agonist (clenbuterol) inhibited endogenous SDF-1 and exogenous bSDF-1 release to the circulation and reduced progenitor cell egress, both during steady state and AMD3100-induced mobilization, while administration of the b2 adrenergic antagonist (propranolol) resulted in opposite effects. Based on our results we propose a model in which egress and mobilization of immature progenitor cells differs from that of maturing leukocytes and is more dependent on SDF-1/CXCR4 interactions. In addition to hematopoietic progenitor cells, also bone marrow stromal cells induce homeostatic secretion of SDF-1, which is increased during mobilization and stress induced recruitment. Secretion of this ligand is also CXCR4-dependent, revealing orchestrated mutual and reciprocal SDF1/CXCR4 interactions and a cross-talk with the nervous system, which regulates progenitor cell egress and recruitment.

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