Homing efficiency and hematopoietic reconstitution of bone marrow-derived stroma cells expanded by recombinant human macrophage-colony stimulating factor in vitro

2004 ◽  
Vol 32 (12) ◽  
pp. 1204-1211 ◽  
Author(s):  
Fu Jin-Xiang ◽  
Shi Xiaofeng ◽  
Qin Jun-Chuan ◽  
Ge Yan ◽  
Zhang Xue-Guang
Keyword(s):  
Bone Marrow ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Hematopoietic Reconstitution ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Recombinant human macrophage colony-stimulating factor (M-CSF) requires subliminal concentrations of granulocyte/macrophage (GM)-CSF for optimal stimulation of human macrophage colony formation in vitro.

1987 ◽  
Vol 166 (6) ◽  
pp. 1851-1860 ◽  
Author(s):  
D Caracciolo ◽  
N Shirsat ◽  
G G Wong ◽  
B Lange ◽  
S Clark ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Colony Formation ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Colony Assay ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Human macrophage colony-stimulating factor (M-CSF or CSF-1), either in purified or in recombinant form, is able to generate macrophagic colonies in a murine bone marrow colony assay, but only stimulates small macrophagic colonies of 40-50 cells in a human bone marrow colony assay. We report here that recombinant human granulocytic/macrophage colony stimulating factor (rhGM-CSF) at concentrations in the range of picograms enhances the responsiveness of bone marrow progenitors to M-CSF activity, resulting in an increased number of macrophagic colonies of up to 300 cells. Polyclonal antiserum against M-CSF did not alter colony formation of bone marrow progenitors incubated with GM-CSF at optimal concentration (1-10 ng/ml) for these in vitro assays. Thus, GM-CSF at higher concentrations (nanogram range) can by itself, elicit macrophagic colonies, and at lower concentrations (picogram range) acts to enhance the responsiveness of these progenitors to M-CSF.

scholarly journals Human macrophage colony-stimulating factor induces macrophage colonies after L-phenylalanine methylester treatment of human marrow

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1783-1787 ◽  
Author(s):  
CS Rosenfeld ◽  
C Evans ◽  
RK Shadduck
Keyword(s):  
Bone Marrow ◽  
Conditioned Media ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Colony Stimulating Activity ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Macrophage-colony stimulating factor (M-CSF) has well-known effects on murine bone marrow, but its colony stimulating activity for human bone marrow is controversial. After treatment of human bone marrow with L- phenylalanine methylester (PME), macrophage-colonies (CFU-M) were induced by M-CSF in a dose-dependent fashion. The optimal concentration of recombinant human-macrophage colony stimulating factor (rhM-CSF) was 1,000 U/mL. Purified human urine M-CSF had colony stimulating activity similar to rhM-CSF. Further studies were performed to determine the factors responsible for the enhanced CFU-M formation from PME treated marrow. Compared with nylon wool and carbonyl iron monocyte depletion methods, PME eliminated significantly more monocytes and myeloid cells. This observation suggested that these cells may release hematopoietic inhibitory factors for CFU-M. Low concentrations (1%) but not normal (10%) concentrations of blood monocytes were inhibitory (mean inhibition, 48%) to CFU-M. High concentrations of monocytes (50%) augmented CFU-M colonies. HL-60 conditioned media was used to simulate secretory products of early myeloid cells. HL-60 conditioned media (1%) inhibited CFU-M formation but not granulocyte macrophage or granulocyte colonies. We conclude that M-CSF has colony stimulating activity for human marrow that can be recognized after removal of inhibitory cells by PME treatment.

scholarly journals Interleukin-33, a Target of Parathyroid Hormone and Oncostatin M, Increases Osteoblastic Matrix Mineral Deposition and Inhibits Osteoclast Formation in Vitro

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1911-1922 ◽  
Author(s):  
Hasnawati Saleh ◽  
Damien Eeles ◽  
Jason M. Hodge ◽  
Geoffrey C. Nicholson ◽  
Ran Gu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Osteoclast Formation ◽  
Oncostatin M ◽  
Colony Stimulating Factor ◽  
Mineral Deposition ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

IL-33 is an important inflammatory mediator in allergy, asthma, and joint inflammation, acting via its receptor, ST2L, to elicit Th2 cell cytokine secretion. IL-33 is related to IL-1 and IL-18, which both influence bone metabolism, IL-18 in particular inhibiting osteoclast formation and contributing to PTH bone anabolic actions. We found IL-33 immunostaining in osteoblasts in mouse bone and IL-33 mRNA expression in cultured calvarial osteoblasts, which was elevated by treatment with the bone anabolic factors oncostatin M and PTH. IL-33 treatment strongly inhibited osteoclast formation in bone marrow and spleen cell cultures but had no effect on osteoclast formation in receptor activator of nuclear factor-κB ligand/macrophage colony-stimulating factor-treated bone marrow macrophage (BMM) or RAW264.7 cultures, suggesting a lack of direct action on immature osteoclast progenitors. However, osteoclast formation from BMM was inhibited by IL-33 in the presence of osteoblasts, T cells, or mature macrophages, suggesting these cell types may mediate some actions of IL-33. In bone marrow cultures, IL-33 induced mRNA expression of granulocyte macrophage colony-stimulating factor, IL-4, IL-13, and IL-10; osteoclast inhibitory actions of IL-33 were rescued only by combined antibody ablation of these factors. In contrast to osteoclasts, IL-33 promoted matrix mineral deposition by long-term ascorbate treated primary osteoblasts and reduced sclerostin mRNA levels in such cultures after 6 and 24 h of treatment; sclerostin mRNA was also suppressed in IL-33-treated calvarial organ cultures. In summary, IL-33 stimulates osteoblastic function in vitro but inhibits osteoclast formation through at least three separate mechanisms. Autocrine and paracrine actions of osteoblast IL-33 may thus influence bone metabolism.

scholarly journals Effects of parenteral recombinant human macrophage colony-stimulating factor on monocyte number, phenotype, and antitumor cytotoxicity in nonhuman primates

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2042-2048 ◽  
Author(s):  
DH Munn ◽  
MB Garnick ◽  
NK Cheung
Keyword(s):  
Nonhuman Primates ◽  
Clinical Symptoms ◽  
Progressive Increase ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Hla Dr ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Recombinant human macrophage colony-stimulating factor (rhM-CSF) was given to cynomolgus monkeys by continuous intravenous infusion or subcutaneous injection, at a dose of 50 to 100 micrograms/kg/d in repetitive 14-day cycles. Starting within 24 to 48 hours of initiation of rhM-CSF, there was a progressive increase in the number of circulating monocytes, from a baseline of 811 +/- 253 cells/microL to a peak of 3,495 +/- 712 cells/microL on day 5 to 7. Many of these cells were large, granular, and extensively vacuolated. The expanded cell population expressed HLA-DR, LFA3, CD11b (904), and CD14 (MY4), and was 77% CD16 (FcRIII) positive by two-color cytofluorometry. In functional assays, fresh monocytes showed little cytotoxicity against cultured human melanoma cells (SKMel-1), with or without prior rhM-CSF treatment. However, after 3 days of in vitro culture in rhM-CSF, monocytes from treated animals mediated efficient antibody-dependent cytotoxicity (ADCC) against SKMel-1 using the murine monoclonal antibody 3F8 (IgG3, anti-ganglioside GD2). Under the same conditions, monocytes from control animals showed little ADCC (17% versus 82%, P less than .05). Antitumor cytotoxicity in the absence of antibody was less efficient and was not significantly different between the two groups. There was a mild decrease in platelet count during rhM-CSF treatment, without clinical symptoms. No abnormalities of serum biochemical parameters were seen. We conclude that parenteral rhM-CSF increases the number of circulating monocytes in nonhuman primates, and that these monocytes mediate increased antitumor ADCC after a brief period of in vitro differentiation. This study has implications for the design of possible future clinical trials combining antitumor monoclonal antibodies and rhM-CSF.

scholarly journals In vivo stimulation of megakaryocytopoiesis by recombinant murine granulocyte-macrophage colony-stimulating factor

Blood ◽  
1990 ◽  
Vol 76 (8) ◽  
pp. 1473-1480
Author(s):  
AM Vannucchi ◽  
A Grossi ◽  
D Rafanelli ◽  
PR Ferrini
Keyword(s):  
Bone Marrow ◽  
Blood Platelets ◽  
Colony Stimulating Factor ◽  
Platelet Production ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Stimulation Of

Murine recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) was injected in mice, and the effects on bone marrow, splenic megakaryocytes, megakaryocyte precursors (megakaryocyte colony-forming units [CFU-Meg]) were evaluated. In mice injected three times a day for 6 days with 12,000 to 120,000 U rGM-CSF, no significant modification of both platelet levels and mean platelet volume was observed, while there was a twofold increase in blood neutrophils. However, the rate of platelet production, as assessed by the measurement of 75selenomethionine incorporation into blood platelets, was On the contrary, administration of up to 384,000 U rGM-CSF two times a day for 2 days, as for a typical “thrombopoietin assay,” failed to modify platelet production. A significant dose-related increase in the number of splenic megakaryocytes occurred in mice receiving 60,000 to 120,000 U rGM-CSF, while a slight increase in the number of bone marrow megakaryocytes was observed in mice injected with 120,000 U rGM-CSF. The proportion of bone marrow megakaryocytes with a size less than 18 microns and greater than 35 microns resulted significantly higher in mice receiving rGM-CSF in comparison with controls; an increase in the percentage of splenic megakaryocytes greater than 35 microns was also observed. A statistically significant increase in the total spleen content of CFU-Meg was observed after administration of 90,000 and 120,000 U rGM-CSF three times a day for 6 days, while no effect on bone marrow CFU-Meg was recorded, irrespective of the dose delivered. Finally, 24 hours after a single intravenous injection of rGM-CSF, there was a significant increase in the proportion of CFU-Meg in S- phase, with the splenic progenitors being more sensitive than bone marrow-derived CFU-Meg. These data indicate that rGM-CSF has in vivo megakaryocyte stimulatory activity, and are consistent with previous in vitro observations. However, an effective stimulation of megakaryocytopoiesis in vivo, bringing about an increase in the levels of blood platelets, may require interaction of rGM-CSF with other cytokines.

scholarly journals Demonstration of a blood-bone marrow barrier to macrophage colony- stimulating factor

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 68-73 ◽  
Author(s):  
RK Shadduck ◽  
A Waheed ◽  
EJ Wing
Keyword(s):  
Bone Marrow ◽  
Hematopoietic Cells ◽  
Serum Levels ◽  
Colony Stimulating Factor ◽  
Apparent Lack ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Several previous studies suggested that murine macrophage colony- stimulating factor (CSF-1) might have impaired access to hematopoietic cells in the marrow. The apparent lack of hematopoietic responses to exogenous CSF and the finding of available or unoccupied CSF receptors despite saturating CSF levels in the serum led to studies of a potential blood-bone marrow barrier for this factor. Groups of mice were injected with pure unlabeled CSF-1 by either intravenous (IV) or intraperitoneal (IP) routes. Marrow and spleen cells were obtained at intervals after injection, held at 0 degree C, and assessed for changes in binding of 125I-CSF. Saturation of all available CSF receptors is achieved in vitro with 100 to 150 U CSF/mL. Despite achieving serum levels of 5,000 to 7,000 U/mL after IV injection of 25,000 units of CSF, less than 50% of the marrow receptors and less than 85% of the splenic receptors were saturated or downregulated. The decline in receptor availability was transient, with return of receptor sites in two to four hours. Increasing the IV dose to 125,000 units increased serum CSF values to approximately 20,000 U/mL and led to a virtual disappearance of available receptors for two to three hours. When administered IP, only approximately 40% of marrow and 80% of splenic receptors were affected for two hours. It was necessary to increase the dose of CSF to 250,000 units IP to saturate or downregulate receptors for three to four hours after injection. These observations indicate a marked blood-bone marrow barrier and lesser blood-spleen barrier for the transfer of serum CSF to responsive hematopoietic cells in vivo.

scholarly journals Human macrophage colony-stimulating factor induces macrophage colonies after L-phenylalanine methylester treatment of human marrow

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1783-1787
Author(s):  
CS Rosenfeld ◽  
C Evans ◽  
RK Shadduck
Keyword(s):  
Bone Marrow ◽  
Conditioned Media ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Colony Stimulating Activity ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Macrophage-colony stimulating factor (M-CSF) has well-known effects on murine bone marrow, but its colony stimulating activity for human bone marrow is controversial. After treatment of human bone marrow with L- phenylalanine methylester (PME), macrophage-colonies (CFU-M) were induced by M-CSF in a dose-dependent fashion. The optimal concentration of recombinant human-macrophage colony stimulating factor (rhM-CSF) was 1,000 U/mL. Purified human urine M-CSF had colony stimulating activity similar to rhM-CSF. Further studies were performed to determine the factors responsible for the enhanced CFU-M formation from PME treated marrow. Compared with nylon wool and carbonyl iron monocyte depletion methods, PME eliminated significantly more monocytes and myeloid cells. This observation suggested that these cells may release hematopoietic inhibitory factors for CFU-M. Low concentrations (1%) but not normal (10%) concentrations of blood monocytes were inhibitory (mean inhibition, 48%) to CFU-M. High concentrations of monocytes (50%) augmented CFU-M colonies. HL-60 conditioned media was used to simulate secretory products of early myeloid cells. HL-60 conditioned media (1%) inhibited CFU-M formation but not granulocyte macrophage or granulocyte colonies. We conclude that M-CSF has colony stimulating activity for human marrow that can be recognized after removal of inhibitory cells by PME treatment.

scholarly journals Demonstration of a blood-bone marrow barrier to macrophage colony- stimulating factor

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 68-73
Author(s):  
RK Shadduck ◽  
A Waheed ◽  
EJ Wing
Keyword(s):  
Bone Marrow ◽  
Hematopoietic Cells ◽  
Serum Levels ◽  
Colony Stimulating Factor ◽  
Apparent Lack ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Several previous studies suggested that murine macrophage colony- stimulating factor (CSF-1) might have impaired access to hematopoietic cells in the marrow. The apparent lack of hematopoietic responses to exogenous CSF and the finding of available or unoccupied CSF receptors despite saturating CSF levels in the serum led to studies of a potential blood-bone marrow barrier for this factor. Groups of mice were injected with pure unlabeled CSF-1 by either intravenous (IV) or intraperitoneal (IP) routes. Marrow and spleen cells were obtained at intervals after injection, held at 0 degree C, and assessed for changes in binding of 125I-CSF. Saturation of all available CSF receptors is achieved in vitro with 100 to 150 U CSF/mL. Despite achieving serum levels of 5,000 to 7,000 U/mL after IV injection of 25,000 units of CSF, less than 50% of the marrow receptors and less than 85% of the splenic receptors were saturated or downregulated. The decline in receptor availability was transient, with return of receptor sites in two to four hours. Increasing the IV dose to 125,000 units increased serum CSF values to approximately 20,000 U/mL and led to a virtual disappearance of available receptors for two to three hours. When administered IP, only approximately 40% of marrow and 80% of splenic receptors were affected for two hours. It was necessary to increase the dose of CSF to 250,000 units IP to saturate or downregulate receptors for three to four hours after injection. These observations indicate a marked blood-bone marrow barrier and lesser blood-spleen barrier for the transfer of serum CSF to responsive hematopoietic cells in vivo.

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