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

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 Tolllike 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 cultureexpanded 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 Tolllike 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.

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[1] Horwitz EM, Le Blanc K, Dominici M, et al. International Society for Cellular Therapy. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 2005; 7: 393-5.

[2] Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9:641-50.

[3] Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005; 105: 1815-22.

[4] Yagi H, Soto-Gutierrez A, Parekkadan B, et al. Mesenchymal stem cells: Mechanisms of immunomodulation and homing. Cell Transplant. 2010; 19: 667-79.

[5] Waterman RS, Tomchuck SL, Henkle SL, et al. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One. 2010; 5: e10088.

[6] Fu X, Liu G, Halim A, et al. Mesenchymal Stem Cell Migration and Tissue Repair. Cells. 2019; 8: 784.

[7] Shirjang S, Mansoori B, Solali S, et al. Toll-like receptors as a key regulator of mesenchymal stem cell function: An upto-date review. Cell Immunol. 2017; 315: 1-10.

[8] Fitzgerald KA, Kagan JC. Toll-like Receptors and the Control of Immunity. Cell. 2020; 180: 1044-1066.

[9] DelaRosa O, Lombardo E. Modulation of adult mesenchymal stem cells activity by toll-like receptors: implications on therapeutic potential. Mediators Inflamm. 2010; 2010: 865601.

[10] Anderlini P, Champlin RE. Biologic and molecular effects of granulocyte colony-stimulating factor in healthy individuals: recent findings and current challenges. Blood. 2008; 111: 1767-72.

[11] de Kruijf EFM, Fibbe WE, van Pel M. Cytokine-induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche. Ann N Y Acad Sci. 2020; 1466: 24-38.

[12] Lapid K, Glait-Santar C, Gur-Cohen S, et al. Egress and Mobilization of Hematopoietic Stem and Progenitor Cells: A dynamic multi-facet process (December 10, 2012), StemBook, ed. The Stem Cell Research Community, StemBook, doi/10.3824/stembook.1.91.1, http://www. stembook.org.

[13] Joo YD, Lee WS, Won HJ, et al. Upregulation of TLR2 expression on G-CSF-mobilized peripheral blood stem cells is responsible for their rapid engraftment after allogeneic hematopoietic stem cell transplantation. Cytokine. 2011; 54: 36-42.

[14] Kastrup J, Ripa RS, Wang Y, et al. Myocardial regeneration induced by granulocyte-colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: a non-invasive alternative for clinical stem cell therapy? Eur Heart J. 2006; 27: 2748-54.

[15] Yu Q, Chen L, You Y, et al. Erythropoietin combined with granulocyte colony stimulating factor enhances MMP-2 expression in mesenchymal stem cells and promotes cell migration. Mol Med Rep. 2011; 4: 31-6.

[16] Gilevich IV, Fedorenko TV, Pashkova IA, et al. Effects of Growth Factors on Mobilization of Mesenchymal Stem Cells. Bull Exp Biol Med. 2017; 162: 684-686.

[17] Ponte AL, Ribeiro-Fleury T, Chabot V, et al. Granulocytecolony-stimulating factor stimulation of bone marrow mesenchymal stromal cells promotes $CD34^+$ cell migration via a matrix metalloproteinase-2-dependent mechanism. Stem Cells Dev. 2012; 21: 3162-72.

[18] de Kruijf EFM, van Hengel I, Perez-Galarza JM, et al. Mesenchymal Stromal Cells Enhance G-CSF-Induced Mobilization of Hematopoietic Stem- and Progenitor Cells. Blood. 2013; 122: 2460.

[19] Tomchuck SL, Zwezdaryk KJ, Coffelt SB, et al. Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells. 2008; 26: 99-107.

[20] Franzke A, Piao W, Lauber J, et al. G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases. Blood. 2003; 102: 734-9.

[21] Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8: 315-7.

[22] Wang X, Cheng Q, Li L, et al. Toll-like receptors 2 and 4 mediate the capacity of mesenchymal stromal cells to support the proliferation and differentiation of $CD34^+$ cells. Exp Cell Res. 2012; 318: 196-206.

[23] Romieu-Mourez R, François M, Boivin MN, et al. Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a pro-inflammatory phenotype. J Immunol. 2009; 182: 7963-73.

[24] Pevsner-Fischer M, Morad V, Cohen-Sfady M, et al. Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood. 2007; 109: 1422-32.

[25] Hwa Cho H, Bae YC, Jung JS. Role of toll-like receptors on human adipose-derived stromal cells. Stem Cells. 2006; 24: 2744-52.

[26] Jafari M, Asghari A, Delbandi AA, et al. Priming TLR3 and TLR4 in human adipose- and olfactory mucosa-derived mesenchymal stromal cells and comparison of their cytokine secretions. Cytotechnology. 2020; 72: 57-68.
Acta Medica-Cover
  • ISSN: 2147-9488
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2012
  • Yayıncı: HACETTEPE ÜNİVERSİTESİ
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