Characterization of ‘adult-type’ mast cells derived from human bone marrow CD34+ cells cultured in the presence of stem cell factor and interleukin-6. Interleukin-4 is not required for constitutive expression of CD54, FcεRIα and chymase, and CD13 expressi

2002 ◽  
Vol 32 (6) ◽  
pp. 872-880 ◽  
Author(s):  
Y. Shimizu ◽  
K. Sakai ◽  
T. Miura ◽  
T. Narita ◽  
H. Tsukagoshi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Constitutive Expression ◽  
Interleukin 4 ◽  
Adult Type ◽  
Cd34 Cells ◽  
Cells Cultured

scholarly journals Human interleukin-4 enhances stromal cell-dependent hematopoiesis: costimulation with stem cell factor

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2189-2196 ◽  
Author(s):  
U Keller ◽  
MJ Aman ◽  
G Derigs ◽  
C Huber ◽  
C Peschel
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Stromal Cell ◽  
Bone Marrow Cells ◽  
Interleukin 4 ◽  
Adherent Cell ◽  
Hematopoietic Progenitors ◽  
Cd34 Cells

Abstract Interleukin-4 (IL-4) has distinct hematopoietic activities, primarily as a costimulant with other cytokines to enhance colony formation of hematopoietic progenitors. We investigated the influence of IL-4 on stromal cell-supported long-term cultures (LTCs) of normal human bone marrow. Addition of IL-4 to LTCs of unseparated bone marrow or highly enriched CD34+ cells resulted in a significant increase of myeloid progenitors in the nonadherent, as well as in the stromal cell-adherent cell populations. In contrast, the total cell number was not influenced by IL-4, suggesting a selective effect on primitive progenitor cells. Cord blood cells or CD34+ bone marrow cells were incubated with stem cell factor (SCF) and/or IL-4 in stromal cell-free cultures. In these experiments, a twofold to fivefold increase of myeloid progenitor cells was observed in the presence of SCF and IL-4 as compared with SCF alone. Preincubation of the stromal cell cultures with IL-4 resulted in an enhanced adherence of CD34+ cells to the stromal layer. Secretion of hematopoietic growth factors produced by the stromal cells, such as granulocyte-macrophage colony-stimulating factor (G-CSF), and IL-1, was inhibited by IL-4. Thus, the increase of hematopoietic progenitors in LTCs, as observed in the presence of IL-4, can be at least partially explained by a costimulation of SCF and IL-4 on primitive progenitor cells and by an enhancement of hematopoietic cells to stroma. The downregulation of CSFs by IL-4 might prevent the expansion of the mature hematopoietic cell compartment.

scholarly journals Human interleukin-4 enhances stromal cell-dependent hematopoiesis: costimulation with stem cell factor

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2189-2196
Author(s):  
U Keller ◽  
MJ Aman ◽  
G Derigs ◽  
C Huber ◽  
C Peschel
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Stromal Cell ◽  
Bone Marrow Cells ◽  
Interleukin 4 ◽  
Adherent Cell ◽  
Hematopoietic Progenitors ◽  
Cd34 Cells

Interleukin-4 (IL-4) has distinct hematopoietic activities, primarily as a costimulant with other cytokines to enhance colony formation of hematopoietic progenitors. We investigated the influence of IL-4 on stromal cell-supported long-term cultures (LTCs) of normal human bone marrow. Addition of IL-4 to LTCs of unseparated bone marrow or highly enriched CD34+ cells resulted in a significant increase of myeloid progenitors in the nonadherent, as well as in the stromal cell-adherent cell populations. In contrast, the total cell number was not influenced by IL-4, suggesting a selective effect on primitive progenitor cells. Cord blood cells or CD34+ bone marrow cells were incubated with stem cell factor (SCF) and/or IL-4 in stromal cell-free cultures. In these experiments, a twofold to fivefold increase of myeloid progenitor cells was observed in the presence of SCF and IL-4 as compared with SCF alone. Preincubation of the stromal cell cultures with IL-4 resulted in an enhanced adherence of CD34+ cells to the stromal layer. Secretion of hematopoietic growth factors produced by the stromal cells, such as granulocyte-macrophage colony-stimulating factor (G-CSF), and IL-1, was inhibited by IL-4. Thus, the increase of hematopoietic progenitors in LTCs, as observed in the presence of IL-4, can be at least partially explained by a costimulation of SCF and IL-4 on primitive progenitor cells and by an enhancement of hematopoietic cells to stroma. The downregulation of CSFs by IL-4 might prevent the expansion of the mature hematopoietic cell compartment.

scholarly journals Cofactors are essential for stem cell factor-dependent growth and maturation of mast cell progenitors: comparative effects of interleukin- 3 (IL-3), IL-4, IL-10, and fibroblasts

Blood ◽  
1995 ◽  
Vol 85 (1) ◽  
pp. 57-65 ◽  
Author(s):  
D Rennick ◽  
B Hunte ◽  
G Holland ◽  
L Thompson-Snipes
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Mast Cells ◽  
Colony Formation ◽  
Stem Cell Factor ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Phenotypic Change ◽  
Interleukin 3

Stem cell factor (SCF) possesses many mast cell-stimulating activities, including the ability to support the growth of mucosal-like mast cells (MMCs) and connective tissue mast cells (CTMCs). However, this study shows that, in the absence of accessory cells, SCF does not stimulate the clonal growth of primitive mast cell progenitors. Nevertheless, SCF exhibited potent growth-promoting effects when combined with the cytokines interleukin-3 (IL-3), interleukin-4 (IL-4), and interleukin- 10 (IL-10). Our comparative studies have shown that optimal mast cell colony formation occurs when both IL-4 and IL-10 are combined with SCF. However, in the presence of SCF, these two cofactors appear to mediate different effects. IL-4 was more efficient than IL-10 in costimulating the initiation of SCF-dependent colony formation by mast cell progenitors and in sustaining the proliferation of newly generated progeny. On the other hand, IL-4 was less efficient than IL-10 in supporting mast cell differentiation, as evidenced by morphology, cell enlargement, and granule production. Although the actions of IL-4 and IL-10 were not equivalent, additional experiments indicated that their ability to serve as early- and late-acting factors, respectively, were complimentary. We have also found that the mast cells generated in colonies stimulated by IL-4, IL-10, and SCF produced high levels of histamine (6–8 pg per cell). None of the mast cells generated in our cultures synthesized heparin. A phenotypic change from safranin- negative to safranin-positive cells associated with heparin-producing CTMCs was accomplished after coculture of the mast cells with fibroblast cell lines derived from normal mice or from SI/SId mice plus soluble factors. Collectively, our observations demonstrate that SCF acts as a competence factor for mast cell progenitor growth. In addition, the ability of SCF to support certain stages of mast cell differentiation is profoundly influenced by interactions with specific cofactors.

Stem cell factor and interleukin-4 increase responsiveness of mast cells to Substance P

2000 ◽  
Vol 28 (6) ◽  
pp. 626-634 ◽  
Author(s):  
Khalil Karimi ◽  
Frank A Redegeld ◽  
Richard Blom ◽  
Frans P Nijkamp
Keyword(s):  
Stem Cell ◽  
Mast Cells ◽  
Substance P ◽  
Stem Cell Factor ◽  
Interleukin 4

Membrane-Bound Human Stem Cell Factor Promotes Differentiation of Human Granulocytes and Mast Cells In Vivo,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3419-3419
Author(s):  
Shinsuke Takagi ◽  
Yoriko Saito ◽  
Atsushi Hijikata ◽  
Satoshi Tanaka ◽  
Takashi Watanabe ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Myeloid Cells ◽  
Human Stem Cell ◽  
Myeloid Development ◽  
Membrane Bound ◽  
Human Stem Cell Factor

Abstract Abstract 3419 Recently, advances in xenograft models for human hemamtopoietic stem cells (HSCs), or the humanized mice, have begun to allow investigators to examine the differentiation of human hematopoietic and immune cells in vivo. However, lymphoid-skewed human hematopoietic development in the mouse bone marrow is one of the remaining limitations in the humanized mouse models. The inefficient human myeloid development could at least partly be attributed to the mouse microenvironment not fully supporting differentiation and maturation of human myeloid lineage. To overcome this problem, we focused on the role of membrane-bound human stem cell factor in supporting the maintenance of human HSCs and inducing the development of human myeloid cells and created human stem cell factor transgenic NOD/SCID/IL2rgKO (hSCF Tg NSG) mice. Transplantation of 5000–50000 cord blood-derived Lin-CD34+CD38- cells resulted in significantly higher engraftment of human CD45+ leukocytes at 3–6 months post-transplantation in the bone marrow, spleen, and peripheral blood of hSCF Tg NSG recipients compared with those of non-transgenic NSG recipients. The enhanced human CD45+ engraftment was most prominent in the bone marrow (hSCF Tg recipients: 98.0 +/− 1.3%, n= 15, non-Tg NSG controls: 75.3 +/− 7.3%, n=7). In the bone marrow, the frequency of human CD33+ myeloid cells within the total human CD45+ population was significantly higher in the hSCF Tg NSG recipients than in the non-Tg NSG recipients and constituted the majority of human hematopoietic cells (hSCF Tg recipients: 54.6 +/− 4.5%, n=15 and non-Tg NSG controls: 29.3 +/− 4.0%, n=7). Flow cytometric analysis demonstrated that the majority of engrafted human myeloid cells in the hSCF Tg recipient bone marrow were side-scatter high, HLA-DR negative granulocytes. Reflecting the effect of human SCF on the development of human mast cells, human c-Kit+CD203c+ mast cells were identified in the bone marrow, spleen, and gastrointestinal tracts of the hSCF Tg NSG recipients. Altogether, the in vivo humanized mouse model demonstrates the essential role of membrane-bound SCF in human myeloid development. The hSCF Tg NSG humanized mice may facilitate the in vivo investigation of human HSCs, myeloid progenitors and mature myeloid lineage. Disclosures: No relevant conflicts of interest to declare.

Long-Term Culture of Human CD34+ Progenitors With FLT3-Ligand, Thrombopoietin, and Stem Cell Factor Induces Extensive Amplification of a CD34−CD14− and a CD34−CD14+ Dendritic Cell Precursor

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2244-2252 ◽  
Author(s):  
Jean-François Arrighi ◽  
Conrad Hauser ◽  
Bernard Chapuis ◽  
Rudolf H. Zubler ◽  
Vincent Kindler
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Fold Increase ◽  
Cell Number ◽  
Interleukin 4 ◽  
Flt3 Ligand ◽  
Gm Csf ◽  
Human Cd34 ◽  
Cd34 Cells

Current in vitro culture systems allow the generation of human dendritic cells (DCs), but the output of mature cells remains modest. This contrasts with the extensive amplification of hematopoietic progenitors achieved when culturing CD34+ cells with FLT3-ligand and thrombopoietin. To test whether such cultures contained DC precursors, CD34+ cord blood cells were incubated with the above cytokines, inducing on the mean a 250-fold and a 16,600-fold increase in total cell number after 4 and 8 weeks, respectively. The addition of stem cell factor induced a further fivefold increase in proliferation. The majority of the cells produced were CD34−CD1a− CD14+(p14+) and CD34−CD1a−CD14−(p14−) and did not display the morphology, surface markers, or allostimulatory capacity of DC. When cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), both subsets differentiated without further proliferation into immature (CD1a+, CD14−, CD83−) macropinocytic DC. Mature (CD1a+, CD14−, CD83+) DCs with high allostimulatory activity were generated if such cultures were supplemented with tumor necrosis factor- (TNF). In addition, p14− cells generated CD14+ cells with GM-CSF and TNF, which in turn, differentiated into DC when exposed to GM-CSF and IL-4. Similar results were obtained with frozen DC precursors and also when using pooled human serum AB+ instead of bovine serum, emphasizing that this system using CD34+ cells may improve future prospects for immunotherapy.

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