Recruitment of primitive peripheral blood cells: synergism of interleukin 12 with interleukin 6 and stem cell factor

We previously reported that CD31bright cells, which were sorted from cultured AC133+ cells of adult peripheral blood cells, differentiated more efficiently into endothelial cells than CD31+ cells or CD31- cells, suggesting that CD31bright cells may be endothelial precursor cells. In this study, we found that CD31bright cells have a strong ability to release cytokines. The mixture of vascular endothelial growth factor (VEGF), thrombopoietin (TPO), and stem cell factor stimulated ex vivo expansion of the total cell number from cultured AC133+ cells of adult peripheral blood cells and cord blood cells, resulting in incrementation of the adhesion cells, in which endothelial nitric oxide synthase and kinase insert domain-containing receptor were positive. Moreover, the mixture of VEGF and TPO increased the CD31bright cell population when compared with VEGF alone or the mixture of VEGF and stem cell factor. These data suggest that TPO is an important growth factor that can promote endothelial precursor cells expansion ex vivo.

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Biologic and clinical aspects of autologous stem cell transplantation with mobilized peripheral blood cells in chronic myelogenous leukemia

Current Oncology Reports ◽

10.1007/s11912-000-0086-9 ◽

2000 ◽

Vol 2 (2) ◽

pp. 144-151 ◽

Cited By ~ 1

Author(s):

Francesco Frassoni

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Peripheral Blood ◽

Blood Cells ◽

Myelogenous Leukemia ◽

Clinical Aspects ◽

Peripheral Blood Cells ◽

Mobilized Peripheral Blood

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Bone marrow collected 14 days after in vivo administration of granulocyte colony-stimulating factor and stem cell factor to mice has 10-fold more repopulating ability than untreated bone marrow

Blood ◽

10.1182/blood.v88.1.89.89 ◽

1996 ◽

Vol 88 (1) ◽

pp. 89-97 ◽

Cited By ~ 114

Author(s):

DM Bodine ◽

NE Seidel ◽

D Orlic

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Peripheral Blood ◽

Blood Cells ◽

Bone Marrow Cells ◽

Peripheral Blood Cells ◽

Equivalent Number ◽

High Level ◽

Stimulating Factor ◽

Marrow Cells

Abstract We have examined the repopulating ability of bone marrow and peripheral blood cells collected immediately and at intervals after treatment of donor mice with the combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). Using a competitive repopulation assay we showed that the repopulating ability of peripheral blood cells was highest immediately after cytokine treatment and declined to normal levels within 6 weeks of the termination of treatment with G-CSF and SCF. In contrast the repopulating ability of bone marrow cells was low immediately after cytokine treatment and increased to levels that were 10-fold or more greater than marrow from untreated mice by 14 days after termination of treatment with G-CSF and SCF. This high level of repopulating activity declined to normal levels by 6 weeks after termination of treatment with G-CSF and SCF. The high level of repopulating ability was confirmed by injecting cells from G- CSF- and SCF-treated donors into unconditioned recipients. Peripheral blood cells collected immediately after treatment with G-CSF and SCF engrafted into unconditioned mice sevenfold better than an equivalent number of bone marrow cells from untreated mice. Likewise, bone marrow cells collected 14 days after treatment of the donor animal with G-CSF and SCF engrafted at 10-fold higher levels than an equivalent number of bone marrow cells from untreated mice. We conclude that the treatment of donor mice with G-CSF and SCF causes a transient increase in the repopulating ability of peripheral blood and later of bone marrow. These observations may have applications to clinical hematopoietic stem cell transplantation.

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Interleukin-6 Directly Modulates Stem Cell Factor-Dependent Development of Human Mast Cells Derived From CD34+Cord Blood Cells

Blood ◽

10.1182/blood.v94.2.496.414k19_496_508 ◽

1999 ◽

Vol 94 (2) ◽

pp. 496-508 ◽

Cited By ~ 1

Author(s):

Tatsuya Kinoshita ◽

Nobukuni Sawai ◽

Eiko Hidaka ◽

Tetsuji Yamashita ◽

Kenichi Koike

Keyword(s):

Mast Cell ◽

Stem Cell ◽

Mast Cells ◽

Cord Blood ◽

Interleukin 6 ◽

Blood Cells ◽

Stem Cell Factor ◽

Flow Cytometric Analysis ◽

Flow Cytometric ◽

Cord Blood Cells

In the present study, we attempted to clarify the effects of interleukin-6 (IL-6) on the growth and properties of human mast cells using cultured mast cells selectively generated by stem cell factor (SCF) from CD34+ cord blood cells. The addition of IL-6 to cultures containing mast cells resulted in a substantial reduction of the number of progenies grown by SCF in the liquid culture. This IL-6–mediated inhibition of mast cell growth may be due in part to the suppression at the precursor level, according to the results of a clonal cell culture assay. Moreover, a flow cytometric analysis showed that the cultured mast cells grown in the presence of SCF+IL-6 had decreased c-kit expression. The exposure of cultured mast cells to SCF+IL-6 also caused substantial increases in the cell size, frequency of chymase-positive cells, and intracellular histamine level compared with the values obtained with SCF alone. The flow cytometric analysis showed low but significant levels of expression of IL-6 receptor (IL-6R) and gp130 on the cultured mast cells grown with SCF. The addition of either anti–IL-6R antibody or anti-gp130 antibody abrogated the biological functions of IL-6. Although IL-4 exerted an effect similar to that of IL-6 on the cultured mast cells under stimulation with SCF, the results of comparative experiments suggest that the two cytokines use different regulatory mechanisms. Taken together, the present findings suggest that IL-6 modulates SCF-dependent human mast cell development directly via an IL-6R-gp130 system.

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Profile of Toll-Like Receptors on Peripheral Blood Cells in Relation to Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2012.09.013 ◽

2013 ◽

Vol 19 (2) ◽

pp. 227-234 ◽

Cited By ~ 7

Author(s):

Cristina Skert ◽

Manuela Fogli ◽

Simone Perucca ◽

Emirena Garrafa ◽

Simona Fiorentini ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Graft Versus Host Disease ◽

Allogeneic Stem Cell Transplantation ◽

Peripheral Blood ◽

Blood Cells ◽

Peripheral Blood Cells ◽

Graft Versus Host ◽

Acute Graft

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X-linked genetic factors regulate hematopoietic stem-cell kinetics in females

Blood ◽

10.1182/blood.v95.7.2449 ◽

2000 ◽

Vol 95 (7) ◽

pp. 2449-2451 ◽

Cited By ~ 76

Author(s):

Kaare Christensen ◽

Marianne Kristiansen ◽

Heidi Hagen-Larsen ◽

Axel Skytthe ◽

Lise Bathum ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Peripheral Blood ◽

Blood Cells ◽

Genetic Factors ◽

Cell Kinetics ◽

Elderly Women ◽

Cell Populations ◽

Peripheral Blood Cells ◽

Hematopoietic Stem

Abstract X inactivation makes females mosaics for 2 cell populations, usually with an approximate 1:1 distribution. Skewing of this distribution in peripheral blood cells is more common among elderly women.1–3 The depletion of hematopoietic stem cells followed by random differentiation may explain the acquired skewing with age.4 However, an animal model suggests that selection processes based on X-linked genetic factors are involved.5 We studied peripheral blood cells from 71 monozygotic twin pairs aged 73 to 93 years and from 33 centenarians, and we found that with age, 1 of the cell populations becomes predominant for most women. We also observed a strong tendency for the same cell line to become predominant in 2 co-twins. This suggests that X-linked genetic factors influence human hematopoietic stem cell kinetics. The fact that females have 2 cell lines with different potentials could be one of the reasons women live longer than men.

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Cellular targets and receptors for interleukin-6 II. Characterization of IL-6 binding and receptors in peripheral blood cells and macrophages

European Journal of Clinical Investigation ◽

10.1111/j.1365-2362.1990.tb01873.x ◽

2008 ◽

Vol 20 (4) ◽

pp. 377-384 ◽

Cited By ~ 16

Author(s):

C. MUNCK PETERSEN ◽

O. DAVIDSEN ◽

S. K. MOESTRUP ◽

O. SONNE ◽

A. NYKJAER ◽

...

Keyword(s):

Interleukin 6 ◽

Peripheral Blood ◽

Blood Cells ◽

Peripheral Blood Cells ◽

Cellular Targets

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Bone marrow collected 14 days after in vivo administration of granulocyte colony-stimulating factor and stem cell factor to mice has 10-fold more repopulating ability than untreated bone marrow

Blood ◽

10.1182/blood.v88.1.89.bloodjournal88189 ◽

1996 ◽

Vol 88 (1) ◽

pp. 89-97 ◽

Cited By ~ 6

Author(s):

DM Bodine ◽

NE Seidel ◽

D Orlic

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Peripheral Blood ◽

Blood Cells ◽

Bone Marrow Cells ◽

Peripheral Blood Cells ◽

Equivalent Number ◽

High Level ◽

Stimulating Factor ◽

Marrow Cells

We have examined the repopulating ability of bone marrow and peripheral blood cells collected immediately and at intervals after treatment of donor mice with the combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). Using a competitive repopulation assay we showed that the repopulating ability of peripheral blood cells was highest immediately after cytokine treatment and declined to normal levels within 6 weeks of the termination of treatment with G-CSF and SCF. In contrast the repopulating ability of bone marrow cells was low immediately after cytokine treatment and increased to levels that were 10-fold or more greater than marrow from untreated mice by 14 days after termination of treatment with G-CSF and SCF. This high level of repopulating activity declined to normal levels by 6 weeks after termination of treatment with G-CSF and SCF. The high level of repopulating ability was confirmed by injecting cells from G- CSF- and SCF-treated donors into unconditioned recipients. Peripheral blood cells collected immediately after treatment with G-CSF and SCF engrafted into unconditioned mice sevenfold better than an equivalent number of bone marrow cells from untreated mice. Likewise, bone marrow cells collected 14 days after treatment of the donor animal with G-CSF and SCF engrafted at 10-fold higher levels than an equivalent number of bone marrow cells from untreated mice. We conclude that the treatment of donor mice with G-CSF and SCF causes a transient increase in the repopulating ability of peripheral blood and later of bone marrow. These observations may have applications to clinical hematopoietic stem cell transplantation.

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Improved Gene Transfer Into Baboon Marrow Repopulating Cells Using Recombinant Human Fibronectin Fragment CH-296 in Combination With Interleukin-6, Stem Cell Factor, FLT-3 Ligand, and Megakaryocyte Growth and Development Factor

Blood ◽

10.1182/blood.v92.6.1878.418k39_1878_1886 ◽

1998 ◽

Vol 92 (6) ◽

pp. 1878-1886 ◽

Cited By ~ 4

Author(s):

Hans-Peter Kiem ◽

Robert G. Andrews ◽

Julia Morris ◽

Laura Peterson ◽

Scott Heyward ◽

...

Keyword(s):

Flow Cytometry ◽

Stem Cell ◽

Gene Transfer ◽

Interleukin 6 ◽

Peripheral Blood ◽

Stem Cell Factor ◽

Growth And Development ◽

Transfer Rates ◽

Development Factor ◽

Marrow Cells

We have used a competitive repopulation assay in baboons to develop improved methods for hematopoietic stem cell transduction and have previously shown increased gene transfer into baboon marrow repopulating cells using a gibbon ape leukemia virus (GALV)-pseudotype retroviral vector (Kiem et al, Blood 90:4638, 1997). In this study using GALV-pseudotype vectors, we examined additional variables that have been reported to increase gene transfer into hematopoietic progenitor cells in culture for their ability to increase gene transfer into baboon hematopoietic repopulating cells. Baboon marrow was harvested after in vivo administration (priming) of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF). CD34-enriched marrow cells were divided into two equal fractions to directly compare transduction efficiencies under different gene transfer conditions. Transduction by either incubation with retroviral vectors on CH-296–coated flasks or by cocultivation on vector-producing cells was studied in five animals; in one animal, transduction on CH-296 was compared with transduction on bovine serum albumin (BSA)-coated flasks. The highest level of gene transfer was obtained after 24 hours of prestimulation followed by 48 hours of incubation on CH-296 in vector-containing medium in the presence of multiple hematopoietic growth factors (interleukin-6, stem cell factor, FLT-3 ligand, and megakaryocyte growth and development factor). Using these conditions, up to 20% of peripheral blood and marrow cells contained vector sequences for more than 20 weeks, as determined by both polymerase chain reaction and Southern blot analysis. Gene transfer rates were higher for cells transduced on CH-296 as compared with BSA or cocultivation. In one animal, we have used a vector expressing a cell surface protein (human placental alkaline phosphatase) and have detected 10% and 5% of peripheral blood cells expressing the transduced gene 2 and 4 weeks after transplantation as measured by flow cytometry. In conclusion, the conditions described here have resulted in gene transfer rates that will allow detection of transduced cells by flow cytometry to facilitate the evaluation of gene expression. The levels of gene transfer obtained with these conditions suggest the potential for therapeutic efficacy in diseases affecting the hematopoietic system. © 1998 by The American Society of Hematology.

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