Volume 35, Issue 3 (June 2024)
Studies in Medical Sciences 2024, 35(3): 192-203 |
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Babadi Akasheh M, Delirazh N, Seyyedi S. EVALUATION OF TOLL-LIKE RECEPTORS (TLRS) AGONISTS-TREATED MOUSE BONE MARROW-DERIVED MESENCHYMAL STEM CELLS AND THEIR CULTURE SUPERNATANT ON NK CELLS’ ACTIVITY AGAINST YAC-1 CELLS. Studies in Medical Sciences 2024; 35 (3) :192-203
URL: http://umj.umsu.ac.ir/article-1-6224-en.html
URL: http://umj.umsu.ac.ir/article-1-6224-en.html
Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran (Corresponding Author) , delirezhn@gmail.com
Abstract: (715 Views)
Background & Aims: Mesenchymal stem cells (MSCs) are multipotent, non-hematopoietic precursor cells that can be found in many adult tissues. The multipotency and immunomodulatory potential of MSCs make these cells a remarkable tool for the treatment of some diseases. It seems that stimulation of toll-like receptors expressed on the surface of mesenchymal stem cells may potentiate the immunomodulatory potential of these cells. This study was conducted to investigate the effects of polarized bone marrow-derived mesenchymal stem cells from mice on the cytotoxic activity of natural killer (NK) cells.
Materials & Methods: MSCs were isolated from the bone marrow of the femur and tibia of NMRI mice. The third passage of cells was treated with LPS and Poly I-C, then the effects of polarized MSCs, as well as their culture supernatant, on the cytotoxic activity of NK cells against lymphoid cancer cells Yac-1 (as target cells), were evaluated using flow cytometry after 12, 24, and 72 hours.
Results: MSCs treated with LPS and Poly I-C, and their respective culture supernatants, decreased the percentage of dead cells (necrosis and apoptosis) (38% and 35% respectively) compared to untreated MSCs (44%). In the case of cell viability, this effect was the opposite; that is, the untreated cells showed higher viability.
Conclusions: Previous studies indicated that MSCs inhibit the expansion and cytotoxicity of NK cells on tumor cells; however, our results revealed that MSCs treated with LPS potentiated the inhibitory effects of MSCs on NK cell activity.
Materials & Methods: MSCs were isolated from the bone marrow of the femur and tibia of NMRI mice. The third passage of cells was treated with LPS and Poly I-C, then the effects of polarized MSCs, as well as their culture supernatant, on the cytotoxic activity of NK cells against lymphoid cancer cells Yac-1 (as target cells), were evaluated using flow cytometry after 12, 24, and 72 hours.
Results: MSCs treated with LPS and Poly I-C, and their respective culture supernatants, decreased the percentage of dead cells (necrosis and apoptosis) (38% and 35% respectively) compared to untreated MSCs (44%). In the case of cell viability, this effect was the opposite; that is, the untreated cells showed higher viability.
Conclusions: Previous studies indicated that MSCs inhibit the expansion and cytotoxicity of NK cells on tumor cells; however, our results revealed that MSCs treated with LPS potentiated the inhibitory effects of MSCs on NK cell activity.
Type of Study: Research |
Subject:
ایمونولوژی
References
1. Lewis WD, Lilly S, Jones KL. Lymphoma: diagnosis and treatment. Am Fam Physician 2020;101(1):34-41. [google scholar]
2. Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell 2004;116(5):639-48. [DOI:10.1016/S0092-8674(04)00208-9] [PMID]
3. Mj S. Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA 1998;95(23):13726-31. [DOI:10.1073/pnas.95.23.13726] [PMID] []
4. Shi Y, Inoue H, Wu JC, Yamanaka S. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 2017;16(2):115-30. [DOI:10.1038/nrd.2016.245] [PMID] []
5. Javanmardi Z, Rezaei FS, Delirezh N, Habbenaghi R. Evaluation of the effect of bone marrow derived stem cells on the initial stages of repair of the deep flexor joints of the fingers in rabbits: a biomechanical and immunohistochemical study. Urmia Med J 2011;22(6):521-9. [URL]
6. Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 2004;8(3):301-16. [DOI:10.1111/j.1582-4934.2004.tb00320.x] [PMID] []
7. Guo S, Huang C, Han F, Chen B, Ding Y, Zhao Y, et al. Gastric cancer mesenchymal stem cells inhibit NK cell function through mTOR signalling to promote tumour growth. Stem Cells Int 2021;2021(1):9989790. [DOI:10.1155/2021/9989790] [PMID] []
8. Mokarizadeh A, Delirezh N, Morshedi A, Farshid AA, Moseibi Q. The effect of exosomes derived from mesenchymal stem cells on the polarization of the immune response of helper T lymphocytes and the clinical picture of autoimmune experimental allergic encephalitis. Urmia Med J 2013;23(2):191-201. [URL]
9. Liu Z, Guo Y, Huang L, Jia Y, Liu H, Peng F, et al. Bone marrow mesenchymal stem cells regulate the dysfunction of NK cells via the T cell immunoglobulin and ITIM domain in patients with myelodysplastic syndromes. Cell Commun Signal 2022;20(1):169. [DOI:10.1186/s12964-022-00985-2] [PMID] []
10. Waterman B, Walker JJ, Swaims C, Shortt M, Todd MS, Machen SM, et al. The efficacy of combined cryotherapy and compression compared with cryotherapy alone following anterior cruciate ligament reconstruction. J Knee Surg 2012;25(02):155-60. [DOI:10.1055/s-0031-1299650] [PMID]
11. Darabi E, Morshedi A, Delirezh N, Tokmechi A, Mokarizadeh A. The effect of peptidoglycan-lipopolysaccharide on the production of nitric oxide by mouse mesenchymal stem cells (MSC) and the induction of apoptosis in activated T cells. Urmia Med J 2012;24(12):996-1004. [URL]
12. Rasmusson I. Immune modulation by mesenchymal stem cells. Exp Cell Res 2006;312(12):2169-79. [DOI:10.1016/j.yexcr.2006.03.019] [PMID]
13. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-γ in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006;24(2):386-98. [DOI:10.1634/stemcells.2005-0008] [PMID]
14. Waterman RS, Henkle SL, Betancourt AM. Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis. 2012. [DOI:10.1371/journal.pone.0045590] [PMID] []
15. Yigitbilek F, Ozdogan E, Abrol N, Park WD, Hansen MJ, Dasari S, et al. Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells. Front Immunol 2022;13:952262. [DOI:10.3389/fimmu.2022.952262] [PMID] []
16. Gonzalez VD, Huang Y-W, Delgado-Gonzalez A, Chen S-Y, Donoso K, Sachs K, et al. High-grade serous ovarian tumor cells modulate NK cell function to create an immune-tolerant microenvironment. Cell Rep 2021;36(9). [DOI:10.1016/j.celrep.2021.109632] [PMID] []
17. Bittencourt RAdC, Pereira HR, Felisbino SL, Murador P, Oliveira APEd, Deffune E. Isolation of bone marrow mesenchymal stem cells. Acta Ortopédica Brasileira 2006;14:22-4. [DOI:10.1590/S1413-78522006000100004]
18. Beyer Nardi N, da Silva Meirelles L. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Stem Cells 2006:249-82. [DOI:10.1007/3-540-31265-X_11]
19. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 2005;106(5):1755-61. [DOI:10.1182/blood-2005-04-1496] [PMID]
20. Soleimani M, Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc 2009;4(1):102-6. [DOI:10.1038/nprot.2008.221] [PMID]
21. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One 2010;5(4):e10088. [DOI:10.1371/journal.pone.0010088] [PMID] []
22. Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 1968;21:77-89. [PMID]
23. Piontek GE, Taniguchi K, Ljunggren H, Grönberg A, Kiessling R, Klein G, et al. YAC-1 MHC class I variants reveal an association between decreased NK sensitivity and increased H-2 expression after interferon treatment or in vivo passage. J Immunol 1985;135(6):4281-8. [DOI:10.4049/jimmunol.135.6.4281] [PMID]
24. Giuliani M, Bennaceur-Griscelli A, Nanbakhsh A, Oudrhiri N, Chouaib S, Azzarone B, et al. TLR ligands stimulation protects MSC from NK killing. Stem Cells 2014;32(1):290-300. [DOI:10.1002/stem.1563] [PMID]
25. Gieseke F, Böhringer J, Bussolari R, Dominici M, Handgretinger R, Müller I. Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells. Blood 2010;116(19):3770-9. [DOI:10.1182/blood-2010-02-270777] [PMID]
26. Bunnell BA, Betancourt AM, Sullivan DE. New concepts on the immune modulation mediated by mesenchymal stem cells. Stem Cell Res Ther 2010;1:1-6. [DOI:10.1186/scrt34] [PMID] []
27. Keating A. Mesenchymal stromal cells: new directions. Cell Stem Cell 2012;10(6):709-16. [DOI:10.1016/j.stem.2012.05.015] [PMID]
28. Chen K, Wang D, Du WT, Han Z-B, Ren H, Chi Y, et al. Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. Clin Immunol 2010;135(3):448-58. [DOI:10.1016/j.clim.2010.01.015] [PMID]
29. Bouffi C, Bony C, Courties G, Jorgensen C, Noel D. IL-6-dependent PGE2 secretion by mesenchymal stem cells inhibits local inflammation in experimental arthritis. PLoS One 2010;5(12):e14247. [DOI:10.1371/journal.pone.0014247] [PMID] []
30. Zhao X, Liu D, Gong W, Zhao G, Liu L, Yang L, et al. The toll-like receptor 3 ligand, poly (I: C), improves immunosuppressive function and therapeutic effect of mesenchymal stem cells on sepsis via inhibiting MiR-143. Stem Cells 2014;32(2):521-33. [DOI:10.1002/stem.1543] [PMID]
31. Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 2006;24(1):74-85. [DOI:10.1634/stemcells.2004-0359] [PMID]
32. Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood 2006;107(4):1484-90. [DOI:10.1182/blood-2005-07-2775] [PMID]
33. Darlan DM, Munir D, Putra A, Alif I, Amalina ND, Jusuf NK, et al. Revealing the decrease of indoleamine 2, 3-dioxygenase as a major constituent for B cells survival post-mesenchymal stem cells co-cultured with peripheral blood mononuclear cell (PBMC) of systemic lupus erythematosus (SLE) patients. Med Glasnik 2022;19(1). [DOI:10.17392/1414-21] [PMID]
34. Tobin LM, Healy M, English K, Mahon BP. Human mesenchymal stem cells suppress donor CD4+ T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease. Clin Exp Immunol 2013;172(2):333-48. [DOI:10.1111/cei.12056] [PMID] []
35. Rozenberg A, Rezk A, Boivin M-N, Darlington PJ, Nyirenda M, Li R, et al. Human mesenchymal stem cells impact Th17 and Th1 responses through a prostaglandin E2 and myeloid-dependent mechanism. Stem Cells Transl Med 2016;5(11):1506-14. [DOI:10.5966/sctm.2015-0243] [PMID] []
36. Uccelli A, Moretta L, Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol 2006;36(10):2566-73. [DOI:10.1002/eji.200636416] [PMID]
37. Blanco B, Herrero‐Sánchez MdC, Rodríguez‐Serrano C, García‐Martínez ML, Blanco JF, Muntión S, et al. Immunomodulatory effects of bone marrow versus adipose tissue‐derived mesenchymal stromal cells on NK cells: Implications in the transplantation setting. Eur J [google scholar]
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