Low-dose radiation (LDR) induces hematopoietic hormesis: LDR-induced mobilization of hematopoietic progenitor cells into peripheral blood circulation

2004 ◽  
Vol 32 (11) ◽  
pp. 1088-1096 ◽  
Author(s):  
Wei Li ◽  
Guanjun Wang ◽  
Jiuwei Cui ◽  
Lu Xue ◽  
Lu Cai
Blood ◽  
1995 ◽  
Vol 86 (7) ◽  
pp. 2842-2848 ◽  
Author(s):  
M Korbling ◽  
YO Huh ◽  
A Durett ◽  
N Mirza ◽  
P Miller ◽  
...  

Abstract Apheresis-derived hematopoietic progenitor cells have recently been used for allogeneic transplantation. Forty-one normal donors were studied to assess the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (12 micrograms/kg/d) on the peripheralization of hematopoietic progenitor cells and lymphoid subsets. The white blood cell, polymorphonuclear cell (PMNC), and lymphocyte concentrations at the peak of rhG-CSF effect in the donor's peripheral blood (PB) exceeded baseline by 6.4-, 8.0-, and 2.2-fold, respectively. Corresponding concentrations of PB CD34+ cells and primitive subsets such as CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells increased by 16.3-fold, 24.2-fold, and 23.2-fold, respectively in eight normal donors. The percentage of CD34+ Thy-1dim and CD34+ Thy- 1dim CD38- cells among CD34+ cells increased as well, suggesting an additional peripheralization effect of rhG-CSF on primitive CD34+ subsets. The preapheresis PB CD34+ and CD34+ Thy-1dim cell concentrations were predictive of their corresponding apheresis yield per liter of donor blood processed PB lymphoid subsets were not significantly affected by rhG-CSF treatment. The mean apheresis-derived yield of CD34+, CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells per kilogram of recipient body weight and per liter of donor blood processed was 48.9 x 10(4) (n = 41), 27.2 x 10(4) (n = 10), and 1.9 x 10(4) (n = 10), respectively. As compared with 43 single bone marrow (BM) harvest, the CD34+ cell yield of peripheral blood progenitor cell allografts of 41 normal donors exceeded that of BM allografts by 3.7- fold and that of lymphoid subsets by 16.1-fold (CD3+), 13.3-fold (CD4+), 27.4-fold (CD8+), 11.0-fold (CD19+), and 19.4-fold (CD56+CD3-). All PBPC allografts were cryopreserved before transplantation. The mean recovery of CD34+ cells after freezing, thawing, and washing out dimethylsulfoxide was 86.6% (n = 31) and the recovery of lymphoid subsets was 115.5% (CD3+), 121.4% (CD4+), 105.6% (CD8+), 118.1% (CD19+), and 102.4% (CD56+CD3-). All donors were related to patients: 39 sibling-to-sibling, 1 parent-to-child, and 1 child-to-parent transplant. Thirty-eight transplants were HLA fully identical, two transplants differed in one and two antigens. Engraftment occurred in 38 recipients; two patients died too early to be evaluated, and one patient did not engraft. The lowest CD34+ cell dose transplanted and resulting in complete and sustained engraftment was 2.5 x 10(6)/kg of recipient body weight.(ABSTRACT TRUNCATED AT 400 WORDS)


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1076-1076
Author(s):  
Martin Hildebrandt ◽  
Markus Schuler ◽  
Kirstin Rautenberg ◽  
Christian Gerecke ◽  
Wolf-Dieter Ludwig

Abstract Hematopoietic progenitor cells are rich in aldehyde dehydrogenase (ALDH) activity, allowing their identification using fluorogenic substrates (Aldefluor®, StemCo Biomedical, Durham, North Carolina) and Fluorescence-activated cell sorting (FACS). We compared the numbers of ALDH+ cells in peripheral blood and progenitor cell harvests with the numbers of CD34-positive cells. Furthermore, we compared the numbers of ALDH+ cells with the kinetics of hematopoietic engraftment following high-dose chemotherapy (HDCT) and transplantation of autologous stem cell harvests (SCT). 25 Patients (Multiple Myeloma, n=10, Hodgkin’s disease, n=3, mantle cell lymphoma, n=3, follicular lymphoma, n=2, T-cell lymphoma, n=3, Burkitt-like lymphoma, n=3) were included in treatment protocols involving high-dose chemotherapy, and received mobilization chemotherapy and G-CSF (10 μg/kg/d s.c.). The numbers of CD34-positive cells were determined daily, and peripheral blood progenitor cell apheresis was initiated when adequate. PBPC collections were performed on an AS 104 cell separator (Fresenius AG, St. Wendel, Germany). Samples of peripheral blood and of progenitor cell harvests were routinely tested for the numbers of CD34-positive cells and ALDH+ cells. The enrichment of CD34-positive cells was calculated and compared to the numbers of ALDH+ cells. 20 patients (Multiple Myeloma, n=10, Hodgkin’s disease, n=3, mantle cell lymphoma, n=3, follicular lymphoma, n=2, T-cell lymphoma, n=2) proceeded to HDCT followed by reinfusion of progenitor cell harvests. The enrichment of ALDH+ cells in the course of apheresis exceeded the enrichment of CD34-positive cells slightly (18,3fold +/−12,8 vs. 15,7fold +/−10,2). The percentage of CD34-negative cells among ALDH+ cells was comparable in peripheral blood and in the harvest, whereas the population of CD34-positive, ALDH−negative cells varied substantially in the peripheral blood (CD34−/ ALDH+: 7,53% +/−5,2% (pB) vs. 6,52% +/−3,9 (harvest); CD34+/ALDH−: 24,6% +/−12,3% (pB) vs. 11,9% +/−9,3% (harvest). Following HDCT and SCT, the numbers of ALDH+ cells and of CD34+ cells in the peripheral blood on the day of apheresis and in the harvests were compared with the reconstitution of the peripheral blood count. In a regression analysis, the number of ALDH+ cells in the peripheral blood on the day of apheresis (p=0,005), the number of ALDH+ cells transfused (p=0,01) and the number of CD34-positive cells transfused (p=0,012) were independent predictors of early recovery of the leukocyte counts. CD34-positive and ALDH+ cells appear to comprise partially different subsets of hematopoietic progenitor cells. The quantitation of ALDH+ cells may allow a more reliable prediction of the numbers of early hematopoietic progenitor cells than the assessment of CD34-positive cells and thus may be of predictive value for the recovery of leukocytes following SCT.


2009 ◽  
Vol 77 (9) ◽  
pp. 4070-4080 ◽  
Author(s):  
J. L. Johns ◽  
K. C. MacNamara ◽  
N. J. Walker ◽  
G. M. Winslow ◽  
D. L. Borjesson

ABSTRACT Infection with Anaplasma phagocytophilum, a gram-negative, lipopolysaccharide (LPS)-negative, obligate intracellular bacterium, results in multiple peripheral blood cytopenias. We hypothesized that infection with this organism would result in decreased bone marrow (BM) function and shifts in hematopoietic progenitor cells (HPCs) and lineage-committed cells in a well-established murine model of infection. HPCs and lineage-committed progenitors were enumerated in the BM and spleen during acute infection. BM cytokine production and BM CXCL12 expression were determined. Infection resulted in peripheral blood bicytopenia, marked decreases in the number of lineage-committed HPCs in the BM along with concurrent increases in the number of lineage-committed HPCs in the spleen, and a mixed, predominantly myelosuppressive BM cytokine environment. There was significant downregulation of CXCL12 in BM cells that may have been partially responsible for changes in HPC trafficking observed. Changes occurred in the absence of direct pathogen infection of BM cells. Hematopoietic lineage assessment demonstrated that there was loss of erythrocytes and B lymphocytes from the BM along with increased granulopoiesis. These changes were accompanied by splenomegaly due to lymphoid hyperplasia and increased hematopoiesis, most notably erythropoiesis. These changes largely mimic well-described inflammation and endotoxin-mediated effects on the BM and spleen; however, the numbers of peripheral blood neutrophils appear to be independently modulated as granulocytic hyperplasia does not result in neutrophilia. Our findings highlight a well-conserved series of events that we demonstrate can be instigated by an LPS-negative pathogen in the absence of an endotoxin-mediated acute proinflammatory response.


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