scholarly journals Expression and Function of Homing-Essential Molecules and Enhanced In Vivo Homing Ability of Human Peripheral Blood-Derived Hematopoietic Progenitor Cells after Stimulation with Stem Cell Factor

Stem Cells ◽  
2004 ◽  
Vol 22 (4) ◽  
pp. 580-589 ◽  
Author(s):  
Christina Hart ◽  
Diana Drewel ◽  
Gunnar Mueller ◽  
Jochen Grassinger ◽  
Matthias Zaiss ◽  
...  
Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4100-4108 ◽  
Author(s):  
N Okumura ◽  
K Tsuji ◽  
Y Ebihara ◽  
I Tanaka ◽  
N Sawai ◽  
...  

We investigated the effects of stem cell factor (SCF) on the migration of murine bone marrow hematopoietic progenitor cells (HPC) in vitro using a modification of the checkerboard assay. Chemotactic and chemokinetic activities of SCF on HPC were evaluated by the numbers of HPC migrated on positive and negative gradients of SCF, respectively. On both positive and negative gradients of SCF, HPC began to migrate after 4 hours incubation, and their numbers then increased time- dependently. These results indicated that SCF functions as a chemotactic and chemokinetic agent for HPC. Analysis of types of colonies derived from the migrated HPC showed that SCF had chemotactic and chemokinetic effects on all types of HPC. When migrating activities of other cytokines were examined, interleukin (IL)-3 and IL-11 also affected the migration of HPC, but the degrees of each effect were lower than that of SCF. The results of the present study demonstrated that SCF is one of the most potent chemotactic and chemokinetic factors for HPC and suggest that SCF may play an important role in the flow of HPC into bone marrow where stromal cells constitutively produce SCF.


Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1720-1723 ◽  
Author(s):  
RA Briddell ◽  
CA Hartley ◽  
KA Smith ◽  
IK McNiece

Abstract Splenectomized mice treated for 7 days with pegylated recombinant rat stem cell factor (rrSCF-PEG) showed a dose-dependent increase in peripheral blood progenitor cells (PBPC) that have enhanced in vivo repopulating potential. A dose of rrSCF-PEG at 25 micrograms/kg/d for 7 days produced no significant increase in PBPC. However, when this dose of rrSCF-PEG was combined with an optimal dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 200 micrograms/kg/d), a synergistic increase in PBPC was observed. Compared with treatment with rhG-CSF alone, the combination of rrSCF-PEG plus rhG-CSF resulted in a synergistic increase in peripheral white blood cells, in the incidence and absolute numbers of PBPC, and in the incidence and absolute numbers of circulating cells with in vivo repopulating potential. These data suggest that low doses of SCF, which would have minimal, if any, effects in vivo, can synergize with optimal doses of rhG-CSF to enhance the mobilization of PBPC stimulated by rhG-CSF alone.


Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1720-1723 ◽  
Author(s):  
RA Briddell ◽  
CA Hartley ◽  
KA Smith ◽  
IK McNiece

Splenectomized mice treated for 7 days with pegylated recombinant rat stem cell factor (rrSCF-PEG) showed a dose-dependent increase in peripheral blood progenitor cells (PBPC) that have enhanced in vivo repopulating potential. A dose of rrSCF-PEG at 25 micrograms/kg/d for 7 days produced no significant increase in PBPC. However, when this dose of rrSCF-PEG was combined with an optimal dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 200 micrograms/kg/d), a synergistic increase in PBPC was observed. Compared with treatment with rhG-CSF alone, the combination of rrSCF-PEG plus rhG-CSF resulted in a synergistic increase in peripheral white blood cells, in the incidence and absolute numbers of PBPC, and in the incidence and absolute numbers of circulating cells with in vivo repopulating potential. These data suggest that low doses of SCF, which would have minimal, if any, effects in vivo, can synergize with optimal doses of rhG-CSF to enhance the mobilization of PBPC stimulated by rhG-CSF alone.


Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3195-3202 ◽  
Author(s):  
GP Reddy ◽  
PJ Quesenberry

Stem cell factor (SCF) is known to act synergistically with other hematopoietic factors in increasing the colony formation of hematopoietic progenitor cells. We have shown that interleukin-3 (IL-3)- dependent proliferation of NFS-60 cells is associated with the induction of a specific calmodulin-binding protein of about 68 kD (CaM- BP68). To evaluate the relationship between proliferative stimulation and the induction of CaM-BP68 by cytokines, we examined whether the increased proliferative potential of NFS-60 cells in response to SCF is reflected in an increased induction of the CaM-BP68. We observed that SCF alone has a limited effect on proliferative stimulation and on the induction of CaM-BP68 in factor-deprived NFS-60 cells. However, when combined with IL-3, granulocyte colony-stimulating factor (G-CSF), or IL-6, it caused a significant increase in cytokine-dependent proliferative stimulation, as well as in the induction of CaM-BP68. Furthermore, an increase in IL-3-dependent induction of CaM-BP68 in the presence of SCF coincided with a corresponding increase in thymidine kinase activity, whose expression is linked to G1/S transition of the cells. At low concentrations SCF caused a synergistic increase in IL-3- dependent induction of both CaM-BP68 and thymidine kinase activity. In contrast to the changes in CaM-BP68 and thymidine kinase activity, no significant changes in DNA polymerase alpha were observed in factor- deprived NFS-60 cells in response to IL-3 and/or SCF. These observations suggest an increased expression of CaM-BP68 and thymidine kinase are associated with the synergistic effect of SCF on factor- dependent proliferation of hematopoietic progenitor cells.


Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 4090-4097 ◽  
Author(s):  
S. Hacein-Bey ◽  
G. De Saint Basile ◽  
J. Lemerle ◽  
A. Fischer ◽  
M. Cavazzana-Calvo

Abstract X-linked severe combined immunodeficiency (SCID-Xl) is a rare human inherited disorder in which early T and natural killer (NK) lymphocyte development is blocked. The genetic disorder results from mutations in the common γc chain that participates in several cytokine receptors including the interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15 receptors. We have shown in a previous report that γc gene transfer into SCID-Xl bone marrow (BM) cells restores efficient NK cell differentiation. In this study, we have focused on the introduction of the γc gene into SCID-Xl hematopoietic stem cells with the goal of obtaining differentiation into mature T cells. For this purpose, we used the in vitro hybrid fetal thymic organ culture (FTOC) system in which a combination of cytokines consisting of stem cell factor (SCF), Flt-3L, IL-7, IL-1, and IL-15 is added concomitantly. In this culture system, CD34+ marrow cells from two SCID-Xl patients were able to mature into double positive CD4+ CD8+ cells and to a lesser degree into CD4+ TCRβ+ single positive cells after retroviral-mediated γc gene transfer. In addition, examination of the output cell population at the TCR DJβ1 locus exhibited multiple rearrangements. These results indicate that restoration of the γc/JAK/STAT signaling pathway during the early developmental stages of thymocytes can correct the T-cell differentiation block in SCID-Xl hematopoietic progenitor cells and therefore establishes a basis for further clinical γc gene transfer studies.


2010 ◽  
Vol 40 (7) ◽  
pp. 711-719 ◽  
Author(s):  
Fumihito Tajima ◽  
Hiroyuki Tsuchiya ◽  
Kenichi Nishikawa ◽  
Motoyuki Kataoka ◽  
Ichiro Hisatome ◽  
...  

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