Secretion of stem cell factor and granulocyte–macrophage colony-stimulating factor by mouse embryos in culture: influence of group culture

Zygote ◽  
2008 ◽  
Vol 16 (4) ◽  
pp. 297-301 ◽  
Author(s):  
A. P. Contramaestre ◽  
F. Sifontes ◽  
R. Marín ◽  
M. I. Camejo
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Culture Medium ◽  
Mouse Embryos ◽  
Colony Stimulating Factor ◽  
Group Culture ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

SummaryPrevious studies showed that the addition of a growth factor to the culture medium could modulate embryo development. The possible secretion of different factors to the culture medium by the embryo itself, however, has been poorly evaluated. The present study was designed to investigate: (1) the influence of single or group culture on the development of 2-cell mouse embryos (strain CD-1) to the blastocyst stage; (2) the release of granulocyte–macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) into the culture medium by the embryo; and (3) the levels of GM-CSF and SCF in the culture medium from both single and group embryos. Two-cell CD-1 mouse embryos were cultured for 96 h singly or in groups of five embryos per drop. GM-CSF and SCF were assayed by ELISA in the complete culture medium. It was found that embryos cultured in groups gave a higher percentage of total blastocyst formation and hatched blastocyst when compared with single embryo culture. The mouse embryos secreted GM-CSF and SCF to the culture medium. The concentration of these cytokines is significantly higher in the group cultures than the level found in single cultures. In conclusion, mouse embryos in culture secrete GM-CSF and SCF to the culture medium and the concentration of these cytokines increases during communal culture. These factors may be operating in both autocrine and paracrine pathways to modulate embryo development during in vitro culture.

scholarly journals Cell-to-cell interaction of cytokine-dependent myeloblastic line constitutively expressing membrane-bound stem cell factor abrogates cytokine dependency partially through granulocyte-macrophage colony- stimulating factor production

Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1220-1228 ◽  
Author(s):  
K Sasaki ◽  
K Ikeda ◽  
K Ogami ◽  
J Takahara ◽  
S Irino
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Cell Interaction ◽  
Colony Stimulating Factor ◽  
Semisolid Medium ◽  
Gm Csf ◽  
Membrane Bound ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Stem cell factor (SCF) is a cytokine for hematopoietic progenitor cells and plays an important role in megakaryocyte proliferation. The UT-7 cell line was established from a patient with megakaryoblastic leukemia, and its growth and survival are strictly dependent on interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), or IL-6. In this study, we showed that SCF also supported the growth of UT-7 in the absence of other cytokines and downregulated the cell surface c-kit receptors. Constitutive expression of SCF by introducing SCF expression vector made UT-7 grow factor-independently in liquid medium, but not in semisolid medium. This SCF-expressing factor-independent UT-7 (UT-7scf9) expressed the membrane bound form of SCF on their surface, but did not secrete detectable amounts of soluble SCF. UT-7scf9 formed aggregates as they grew in the absence of cytokines, and this aggregation was inhibited by adding soluble SCF into the medium. UT-7 cultured with SCF and UT-7scf9 cultured without cytokines expressed GM-CSF, and anti-GM-CSF neutralizing antibody partially inhibited their growth. These results suggest that SCF stimulated UT-7 proliferation partially through the autocrine-loop of GM-CSF, and UT-7scf9 expressed SCF mostly as a membrane-bound form, which transduces its growth signal through c-kit receptor as they aggregate by cell-to-cell interaction.

Serum Levels of Granulocyte-Macrophage-colony-stimulating Factor and Stem-cell Factor During Liver Regeneration after Partial Hepatectomy in Humans

2020 ◽  
Vol 15 (2) ◽  
pp. 131-136
Author(s):  
Diego Fiume ◽  
Ilaria Lenci ◽  
Martina Milana ◽  
Tommaso M. Manzia ◽  
Renato Massoud ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Regeneration ◽  
Liver Tumor ◽  
Stem Cell Factor ◽  
Serum Levels ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Background: Multiple biological functions have been recognized regarding Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Stem Cell Factor (SCF). Aim: To evaluate the serum changes of GM-CSF and SCF in patients undergoing surgical resection for liver tumor, in the regenerative phase after surgery in order to identify the possible relationship with the patient, tumor or surgical variables. Methods: Thirty-two consecutive patients (50% male, median age 66), undergoing hepatic resection of liver neoplasm, were evaluated. The liver tumor was Hepatocellular Carcinoma (HCC) in 44% of cases. Other tumors were cholangiocarcinoma and metastasis. Serum levels of GM-CSF and SCF were assessed at baseline and 2 days, 7 days and 4 weeks after surgery. Personal and clinical patient data were also recorded. The statistical analysis was carried out using t-test for unpaired data or ANOVA (repeated measure) for continuous variables and Fisher test for discrete variables. Results: GM-CSF levels remained constant after surgery and were compared to baseline values. SCF levels, on the other hand, increased during the time, after surgery. The evaluation of SCF levels (fold increase) according to surgical, patient and tumor variables evidenced some differences. At day 7 and week 4, SCF levels were statistically increased: i) in patients undergoing a large resection in comparison with others (p<0.05); ii) in patients non-cirrhotic in comparison with cirrhotic ones (p=0.02) and finally; iii) in patients with non-HCC tumor in comparison with HCC ones (p=0.02). Conclusions: During liver regeneration in humans, SCF serum levels are increased allowing to hypothesize a possible role of this chemokine during tissue growth and remodeling.

scholarly journals Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding

1994 ◽  
Vol 14 (12) ◽  
pp. 8432-8437
Author(s):  
B Tang ◽  
H Mano ◽  
T Yi ◽  
J N Ihle
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Amino Terminal ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Stem cell factor (SCF) plays a crucial role in hematopoiesis through its interaction with the receptor tyrosine kinase c-kit. However, the signaling events that are activated by this interaction and involved in the control of growth or differentiation are not completely understood. We demonstrate here that Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through a region that contains a proline-rich motif, amino terminal of the SH3 domain. Following SCF binding, Tec is tyrosine phosphorylated and its in vitro kinase activity is increased. Tyrosine phosphorylation of Tec is not detected in the response to other cytokines controlling hematopoiesis, including colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3). Conversely, the cytoplasmic kinase JAK2 is activated by IL-3 but not by SCF stimulation. The activation of distinct cytoplasmic kinases may account for the synergy seen in the actions of SCF and IL-3 on hematopoietic stem cells.

scholarly journals Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding.

1994 ◽  
Vol 14 (12) ◽  
pp. 8432-8437 ◽  
Author(s):  
B Tang ◽  
H Mano ◽  
T Yi ◽  
J N Ihle
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Amino Terminal ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Stem cell factor (SCF) plays a crucial role in hematopoiesis through its interaction with the receptor tyrosine kinase c-kit. However, the signaling events that are activated by this interaction and involved in the control of growth or differentiation are not completely understood. We demonstrate here that Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through a region that contains a proline-rich motif, amino terminal of the SH3 domain. Following SCF binding, Tec is tyrosine phosphorylated and its in vitro kinase activity is increased. Tyrosine phosphorylation of Tec is not detected in the response to other cytokines controlling hematopoiesis, including colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3). Conversely, the cytoplasmic kinase JAK2 is activated by IL-3 but not by SCF stimulation. The activation of distinct cytoplasmic kinases may account for the synergy seen in the actions of SCF and IL-3 on hematopoietic stem cells.

scholarly journals Premature expression of the macrophage colony-stimulating factor receptor on a multipotential stem cell line does not alter differentiation lineages controlled by stromal cells used for coculture.

1991 ◽  
Vol 173 (5) ◽  
pp. 1267-1279 ◽  
Author(s):  
T Kinashi ◽  
K H Lee ◽  
M Ogawa ◽  
K Tohyama ◽  
K Tashiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stromal Cells ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Colony Stimulating Factor ◽  
Stem Cell Line ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

We are interested to know whether expression of a lineage-specific growth factor receptor is deterministic to lineage commitment during hematopoiesis. For this purpose, we introduced the human c-fms gene into the multipotential stem cell clone LyD9 and two myeloid progenitor clones, L-GM3 and L-G3, cells that differentiate in response to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte (G)-CSF, respectively. Although LyD9 cells have differentiation potential to become macrophages, c-fms transfectants of LyD9 and L-GM3 cells did not differentiate in response to human macrophage (M)-CSF. However, c-fms transfectants of L-G3 cells differentiated to neutrophils in response to human M-CSF. These results indicate that the M-CSF receptor requires a specific signal transduction pathway to exert its differentiational and proliferative effects. Furthermore, the M-CSF receptor can convey a granulocyte-type differentiation signal possibly by cooperating with the G-CSF receptor signal transduction pathway. The c-fms-transfected LyD9 cells as well as the original LyD9 cells differentiated predominantly into GM-CSF- and G-CSF-responsive cells by coculturing with PA6 and ST2 stromal cells, respectively. The results indicate that differentiation lineage is not affected by premature expression of the M-CSF receptor. Instead, the stromal cell used for coculture apparently controls lineage-selective differentiation of the multi-potential stem cell line.

Phase I Study of Chimeric Human/Murine Anti–Ganglioside GD2Monoclonal Antibody (ch14.18) With Granulocyte-Macrophage Colony-Stimulating Factor in Children With Neuroblastoma Immediately After Hematopoietic Stem-Cell Transplantation: A Children’s Cancer Group Study

2000 ◽  
Vol 18 (24) ◽  
pp. 4077-4085 ◽  
Author(s):  
M. Fevzi Ozkaynak ◽  
Paul M. Sondel ◽  
Mark D. Krailo ◽  
Jacek Gan ◽  
Brad Javorsky ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Neuroblastoma Cells ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE: Ganglioside GD2is strongly expressed on the surface of human neuroblastoma cells. It has been shown that the chimeric human/murine anti-GD2monoclonal antibody (ch14.18) can induce lysis of neuroblastoma cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The purposes of the study were (1) to determine the maximum-tolerated dose (MTD) of ch14.18 in combination with standard dose granulocyte-macrophage colony-stimulating factor (GM-CSF) for patients with neuroblastoma who recently completed hematopoietic stem-cell transplantation (HSCT), and (2) to determine the toxicities of ch14.18 with GM-CSF in this setting.PATIENTS AND METHODS: Patients became eligible when the total absolute phagocyte count (APC) was greater than 1,000/μL after HSCT. ch14.18 was infused intravenously over 5 hours daily for 4 consecutive days. Patients received GM-CSF 250 μg/m2/d starting at least 3 days before ch14.18 and continued for 3 days after the completion of ch14.18. The ch14.18 dose levels were 20, 30, 40, and 50 mg/m2/d. In the absence of progressive disease, patients were allowed to receive up to six 4-day courses of ch14.18 therapy with GM-CSF. Nineteen patients with neuroblastoma were treated.RESULTS: A total of 79 courses were administered. No toxic deaths occurred. The main toxicities were severe neuropathic pain, fever, nausea/vomiting, urticaria, hypotension, mild to moderate capillary leak syndrome, and neurotoxicity. Three dose-limiting toxicities were observed among six patients at 50 mg/m2/d: intractable neuropathic pain, grade 3 recurrent urticaria, and grade 4 vomiting. Human antichimeric antibody developed in 28% of patients.CONCLUSION: ch14.18 can be administered with GM-CSF after HSCT in patients with neuroblastoma with manageable toxicities. The MTD is 40 mg/m2/d for 4 days when given in this schedule with GM-CSF.

Effect of Granulocyte-Macrophage Colony-Stimulating Factor on Prevention and Treatment of Invasive Fungal Disease in Recipients of Allogeneic Stem-Cell Transplantation: A Prospective Multicenter Randomized Phase IV Trial

2015 ◽  
Vol 33 (34) ◽  
pp. 3999-4006 ◽  
Author(s):  
Liping Wan ◽  
Yicheng Zhang ◽  
Yongrong Lai ◽  
Ming Jiang ◽  
Yongping Song ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Invasive Fungal Disease ◽  
Colony Stimulating Factor ◽  
Cumulative Mortality ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Related Mortality

Purpose For recipients of allogeneic hematopoietic stem-cell transplantation (alloHSCT), we hypothesized that prophylactic therapy during neutropenia with granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases invasive fungal disease (IFD). Patients and Methods We randomly assigned 206 patients undergoing alloHSCT to receive once-daily subcutaneous GM-CSF (5 to 7 μg/kg per day), granulocyte colony-stimulating factor (G-CSF; 5 to 7 μg/kg per day), or a combination of G-CSF and GM-CSF (2 to 3 μg/kg per day each). Treatment was started on day 5 after transplantation and was continued until the absolute neutrophil count was ≥ 1.5 × 109/L for 2 consecutive days. The primary outcomes were 100-day incidence of proven and probable IFD and response rate of antifungal treatment. Results For the intent-to-treat population, there was no significant difference in 100-day incidences of proven and probable IFD among the three groups. The antifungal treatment response was better in the GM-CSF group and G-CSF+GM-CSF group than in G-CSF group from day 22 to day 100 (P = .009). The 100-day cumulative mortality after transplantation was lower in the GM-CSF group than in the G-CSF group (10.3% v 24.6%, respectively; P = .037). The GM-CSF and G-CSF+GM-CSF groups had lower 100-day transplantation-related mortality than the G-CSF group (8.8%, 8.7%, and 21.7%, respectively; P = .034). After a median follow-up of 600 days, IFD-related mortality was lower in the groups that received GM-CSF or G-CSF+GM-CSF compared with G-CSF (1.47%, 1.45%, and 11.59%, respectively; P = .016). There were no significant differences in relapse, graft-versus-host disease, or hemorrhage-related mortality among the three groups of patients. Conclusion For recipients of alloHSCT, compared with G-CSF, prophylactic GM-CSF was associated with lower 100-day transplantation-related mortality, lower 100-day cumulative mortality, and lower 600-day IFD-related mortality.

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