Volume 19, Issue 1 (January 2021)                   IJRM 2021, 19(1): 75-86 | Back to browse issues page


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Nikoo S, Ebtekar M, Jeddi-Tehrani M, Bozorgmehr M, Zarnani A H. Culture density of menstrual blood-derived stromal/stem cells determines the quality of T cell responses: An experimental study. IJRM 2021; 19 (1) :75-86
URL: http://ijrm.ir/article-1-1736-en.html
1- Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.
2- Department of Immunology, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran.
3- Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
4- Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.
5- Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. , zarnania@gmail.com
Abstract:   (1762 Views)
Background: Menstrual blood-derived stromal/stem cells (MenSCs) are a new population of refreshing and highly proliferative stem cells. Immunomodulatory effects of MenSCs profoundly depend on their relative density.
Objective: To find whether MenSCs cultured at varying numbers would differentially affect the allogenic peripheral blood mononuclear cells (PBMCs) key features.
Materials and Methods: PBMCs were co-cultured with various MenSCs numbers. PBMCs proliferation was investigated via 3H-thymidine incorporation. Flow cytometry was used to assess human leukocyte antigen (HLA)-DR, HLA-ABC, HLA-G, and co-stimulatory markers on MenSCs and the percentage of regulatory T cells (Tregs) among PBMCs. The concentration of cytokines was determined in supernatant of co-cultures.
Results: The support of PBMCs proliferation at low MenSCs densities correlated with higher levels of pro-inflammatory interferon gamma (IFN-γ) in MenSCs/PBMCs co-culture and increased expression of HLA-DR by MenSCs. On the other hand, the suppressive property of MenSCs at higher densities was independent of Treg frequency, but correlated with a high concentration of Interleukin (IL)-6 and IL-10 in the co-cultures.
Conclusion: Totally, at different seeding densities, MenSCs could differentially interact with PBMCs leading to significant changes in the level of anti- and/or pro-inflammatory factors. These preliminary in vitro results are suggested to be taken into consideration in experimental models of MenSC-based immunomodulation. Nonetheless, for efficient utilization of MenSCs anti-inflammatory features in pre-clinical disease models, we still need to broaden our knowledge on MenSC-immune system cross-talk; this could play a part in designing more optimized MenSCs injection modalities in the case of future pre-clinical and subsequently clinical settings.

 
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Type of Study: Original Article | Subject: Stem Cell & Cloning

References
1. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71-74. [DOI:10.1126/science.276.5309.71] [PMID]
2. Brooke G, Cook M, Blair Ch, Han R, Heazlewood C, Jones B, et al. Therapeutic applications of mesenchymal stromal cells. Semin Cell Dev Biol 2007; 18: 846-858. [DOI:10.1016/j.semcdb.2007.09.012] [PMID]
3. Ghannam S, Pene J, Moquet-Torcy G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol 2010; 185: 302-312. [DOI:10.4049/jimmunol.0902007] [PMID]
4. Le Blanc K, Tammik Ch, Rosendahl K, Zetterberg E, Ringden O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003; 31: 890-896. [DOI:10.1016/S0301-472X(03)00110-3]
5. Maccario R, Podesta M, Moretta A, Cometa A, Comoli P, Montagna D, et al. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 2005; 90: 516-525.
6. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006; 24: 1294-1301. [DOI:10.1634/stemcells.2005-0342] [PMID]
7. Nikoo Sh, Ebtekar M, Jeddi-Tehrani M, Shervin A, Bozorgmehr M, Kazemnejad S, et al. Effect of menstrual blood-derived stromal stem cells on proliferative capacity of peripheral blood mononuclear cells in allogeneic mixed lymphocyte reaction. J Obstet Gynaecol Res 2012; 38: 804-809. [DOI:10.1111/j.1447-0756.2011.01800.x] [PMID]
8. Kazemnejad S, Zarnani AH, Khanmohammadi M, Mobini S. Chondrogenic differentiation of menstrual blood-derived stem cells on nanofibrous scaffolds. In: Turksen K, editor. Stem Cell Nanotechnology: Methods and Protocols. Totowa, NJ: Humana Press; 2013. p. 149-69. [DOI:10.1007/7651_2013_9] [PMID]
9. Nikoo Sh, Ebtekar M, Jeddi-Tehrani M, Shervin A, Bozorgmehr M, Vafaei S, et al. Menstrual blood-derived stromal stem cells from women with and without endometriosis reveal different phenotypic and functional characteristics. Mol Hum Reprod 2014; 20: 905-918. [DOI:10.1093/molehr/gau044] [PMID]
10. Murphy MP, Wang H, Patel AN, Kambhampati S, Angle N, Chan K, et al. Allogeneic endometrial regenerative cells: an "off the shelf solution" for critical limb ischemia? J Translat Med 2008; 6: 45-52. [DOI:10.1186/1479-5876-6-45] [PMID] [PMCID]
11. Najar M, Rouas R, Raicevic G, Boufker HI, Lewalle P, Meuleman N, et al. Mesenchymal stromal cells promote or suppress the proliferation of T lymphocytes from cord blood and peripheral blood: the importance of low cell ratio and role of interleukin-6. Cytotherapy 2009; 11: 570-583. [DOI:10.1080/14653240903079377] [PMID]
12. Fang L, Lange C, Engel M, Zander AR, Fehse B. Sensitive balance of suppressing and activating effects of mesenchymal stem cells on T-cell proliferation. Transplantation 2006; 82: 1370-1373. [DOI:10.1097/01.tp.0000232450.62408.f9] [PMID]
13. Bozorgmehr M, Moazzeni SM, Salehnia M, Sheikhian A, Nikoo Sh, Zarnani AH. Menstrual blood-derived stromal stem cells inhibit optimal generation and maturation of human monocyte-derived dendritic cells. Immunol Lett 2014; 162: 239-246. [DOI:10.1016/j.imlet.2014.10.005] [PMID]
14. Zhong Zh, Patel AN, Ichim ThE, Riordan NH, Wang H, Min WP, et al. Feasibility investigation of allogeneic endometrial regenerative cells. J Transl Med 2009; 7: 15-21. [DOI:10.1186/1479-5876-7-15] [PMID] [PMCID]
15. Lv Y, Xu X, Zhang B, Zhou G, Li H, Du C, et al. Endometrial regenerative cells as a novel cell therapy attenuate experimental colitis in mice. J Transl Med 2014; 12: 344-354. [DOI:10.1186/s12967-014-0344-5] [PMID] [PMCID]
16. Luz‐Crawford P, Torres MJ, Noël D, Fernandez A, Toupet K, Alcayaga‐Miranda F, et al. The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases. Stem Cells 2016; 34: 456-469. [DOI:10.1002/stem.2244] [PMID]
17. Khoury M, Alcayaga-Miranda F, Illanes SE, Figueroa FE. The promising potential of menstrual stem cells for antenatal diagnosis and cell therapy. Front Immunol 2014; 5: 205-212. [DOI:10.3389/fimmu.2014.00205] [PMID] [PMCID]
18. Joo SY, Cho KA, Jung YJ, Kim HS, Park SY, Choi YB, et al. Mesenchymal stromal cells inhibit graft-versus-host disease of mice in a dose-dependent manner. Cytotherapy 2010; 12: 361-370. [DOI:10.3109/14653240903502712] [PMID]
19. Chan JL, Tang KC, Patel AP, Bonilla LM, Pierobon N, Ponzio NM, et al. Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-γ. Blood 2006; 107: 4817-4824. [DOI:10.1182/blood-2006-01-0057] [PMID] [PMCID]
20. Wang H, Jin P, Sabatino M, Ren J, Civini S, Bogin V, et al. Comparison of endometrial regenerative cells and bone marrow stromal cells. J Transl Med 2012; 10: 207-220. [DOI:10.1186/1479-5876-10-207] [PMID] [PMCID]
21. Akira Sh, Hirano T, Taga T, Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J 1990; 4: 2860-2867. [DOI:10.1096/fasebj.4.11.2199284]
22. Del Prete G, De Carli M, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S. Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 1993; 150: 353-360.
23. Melief SM, Schrama E, Brugman MH, Tiemessen MM, Hoogduijn MJ, Fibbe WE, et al. Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti‐inflammatory macrophages. Stem Cells 2013; 31: 1980-1991. [DOI:10.1002/stem.1432] [PMID]
24. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105: 1815-1822. [DOI:10.1182/blood-2004-04-1559] [PMID]
25. Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 1998; 101: 311-320. [DOI:10.1172/JCI1368] [PMID] [PMCID]
26. Eljaafari A, Tartelin ML, Aissaoui H, Chevrel G, Osta B, Lavocat F, et al. Bone marrow-derived and synovium‐derived mesenchymal cells promote Th17 cell expansion and activation through caspase 1 activation: Contribution to the chronicity of rheumatoid arthritis. Arthritis Rheum 2012; 64: 2147-2157. [DOI:10.1002/art.34391] [PMID]
27. Guo Zh, Zheng C, Chen Zh, Gu D, Du W, Ge J, et al. Fetal BM‐derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells. Eur J Immunol 2009; 39: 2840-2849. [DOI:10.1002/eji.200839070] [PMID]
28. Desai MB, Gavrilova T, Liu J, Patel SA, Kartan S, Greco SJ, et al. Pollen-induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis. Clin Transl Immunol 2013; 2: e7. 1-9. [DOI:10.1038/cti.2013.9] [PMID] [PMCID]
29. Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, et al. Human leukocyte antigen‐G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+ CD25highFOXP3+ regulatory T cells. Stem Cells 2008; 26: 212-222. [DOI:10.1634/stemcells.2007-0554] [PMID]
30. Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell 2013; 13: 392-402. [DOI:10.1016/j.stem.2013.09.006] [PMID]
31. Chang ChJ, Yen ML, Chen YCh, Chien ChCh, Huang HI, Bai ChH, et al. Placenta‐derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon‐γ. Stem Cells 2006; 24: 2466-2477. [DOI:10.1634/stemcells.2006-0071] [PMID]
32. Chen PM, Yen ML, Liu KJ, Sytwu HK, Yen BL. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells. J Biomed Sci 2011; 18: 49-59. [DOI:10.1186/1423-0127-18-49] [PMID] [PMCID]
33. Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, et al. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci USA 2009; 106: 4793-4798. [DOI:10.1073/pnas.0900408106] [PMID] [PMCID]
34. Ayyoub M, Deknuydt F, Raimbaud I, Dousset C, Leveque L, Bioley G, et al. Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the TH17 lineage-specific transcription factor RORγt. Proc Natl Acad Sci USA 2009; 106: 8635-8640. [DOI:10.1073/pnas.0900621106] [PMID] [PMCID]
35. Nasef A, Mathieu N, Chapel A, Frick J, François S, Mazurier C, et al. Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation 2007; 84: 231-237. [DOI:10.1097/01.tp.0000267918.07906.08] [PMID]

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