scholarly journals Toll-Like Receptor Expression of Mesenchymal Stem Cells Derived from Granulocyte Colony-Stimulating Factor Treated Bone Marrow Donors

Acta Medica ◽  
2020 ◽  
Vol 51 (4) ◽  
pp. 33-40
Author(s):  
Tekin Aksu ◽  
Neslihan Karakurt ◽  
İrem Akar ◽  
Yasin Köksal ◽  
Fatih M. Azık ◽  
...  

Objective: The present study was planned to examine the expression of Toll-like receptors on human marrow-derived mesenchymal stem cells as a result of in-vivo exposure to granulocyte colony-stimulating factor with or without exposure of the cells to Toll-like receptors agonists. Materials and Methods: Toll-like receptor 2, 3, and 4 expressions of mesenchymal stem cells obtained from healthy human bone marrow donors exposed to in-vivo granulocyte colony-stimulating factor were analyzed, and granulocyte colony-stimulating factor untreated donors served as controls. Also, mesenchymal stem cells were stimulated in-vitro by Toll-like receptor agonists to observe the changes in the expression of the Toll-like receptors. Results: Mesenchymal stem cells obtained from both granulocyte colony-stimulating factor exposed or unexposed donors showed a low level of Toll-like receptor 2, 4 expressions by flow cytometry, whereas Toll-like receptor 3 expression was higher. Lipopolysaccharide was used as an agonist, but no significant difference was observed in the Toll-like receptor 2, 4 expressions, both in the granulocyte colony-stimulating factor exposed and unexposed groups. Stimulation of cells with Toll-like receptor 3 ligand was associated with a statistically significant decrease in Toll-like receptor 3 expressions, which was more profound in granulocyte colony-stimulating factor unexposed cells. Conclusion: We have shown that human bone marrow-derived culture-expanded mesenchymal stem cells express Toll-like receptor 3, whether in-vivo granulocyte colony-stimulating factor treated or untreated. Besides, the Toll-like receptor 3 agonist’s effect in lowering the expression levels was more significant in cells that were not exposed to granulocyte colony-stimulating factor. Additionally, detection of low expression of the pro-inflammatory Toll-like receptor 4 versus higher levels of Toll-like receptor 3 supports literature regarding the immunosuppressive characteristics of marrow-derived mesenchymal stem cells. Modulation of the expression of the Toll-like receptor of mesenchymal stem cells with granulocyte colony-stimulating factor or agonists may have implications in allogeneic mesenchymal stem cell therapies.

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 563-569 ◽  
Author(s):  
G Molineux ◽  
Z Pojda ◽  
TM Dexter

Abstract Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induces leukocytosis in vivo in both intact and splenectomized mice. Full dose response data showed a plateau in this effect at doses over 500 micrograms rhG-CSF/kg body weight/d in intact mice. The effect is magnified in splenectomized mice, where leukocyte numbers reach 100 x 10(6) mL after 4 days' treatment at 250 micrograms/kg/d. Further hematopoietic precursor populations are also affected in both marrow and the spleen; in general, marrow parameters were depressed, while splenic populations were enlarged. In splenectomized mice, both blood- borne stem cells were enhanced, and foci of extramedullary hematopoiesis were enlarged in addition to the effects seen in intact mice. In the marrow of splenectomized and intact mice treated with a high dose of G-CSF, erythroid suppression in the marrow was confirmed with radioactive iron. Our studies confirm and extend previous work on the mode of action of G-CSF, and indicate that side effects of high dose G-CSF therapy might include erythroid suppression in the bone marrow.


Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 563-569 ◽  
Author(s):  
G Molineux ◽  
Z Pojda ◽  
TM Dexter

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induces leukocytosis in vivo in both intact and splenectomized mice. Full dose response data showed a plateau in this effect at doses over 500 micrograms rhG-CSF/kg body weight/d in intact mice. The effect is magnified in splenectomized mice, where leukocyte numbers reach 100 x 10(6) mL after 4 days' treatment at 250 micrograms/kg/d. Further hematopoietic precursor populations are also affected in both marrow and the spleen; in general, marrow parameters were depressed, while splenic populations were enlarged. In splenectomized mice, both blood- borne stem cells were enhanced, and foci of extramedullary hematopoiesis were enlarged in addition to the effects seen in intact mice. In the marrow of splenectomized and intact mice treated with a high dose of G-CSF, erythroid suppression in the marrow was confirmed with radioactive iron. Our studies confirm and extend previous work on the mode of action of G-CSF, and indicate that side effects of high dose G-CSF therapy might include erythroid suppression in the bone marrow.


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Wen-Ching Tzaan ◽  
Hsien-Chih Chen

Intervertebral disc (IVD) degeneration is a multifactorial process that is influenced by contributions from genetic predisposition, the aging phenomenon, lifestyle conditions, biomechanical loading and activities, and other health factors (such as diabetes). Attempts to decelerate disc degeneration using various techniques have been reported. However, to date, there has been no proven technique effective for broad clinical application. Granulocyte colony-stimulating factor (GCSF) is a growth factor cytokine that has been shown to enhance the availability of circulating hematopoietic stem cells to the brain and heart as well as their capacity for mobilization of mesenchymal bone marrow stem cells. GCSF also exerts significant increases in circulating neutrophils as well as potent anti-inflammatory effects. In our study, we hypothesize that GCSF can induce bone marrow stem cells differentiation and mobilization to regenerate the degenerated IVD. We found that GCSF had no contribution in disc regeneration or maintenance; however, there were cell proliferation within end plates. The effects of GCSF treatment on end plates might deserve further investigation.


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