The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation


1 Department of Immunology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

2 Departments of Anatomical Sciences and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored.
Materials and Methods: In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay.
Results: In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells.
Conclusion: This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications.


1. Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007;110:3499-506.  Back to cited text no. 1
2. Stagg J, Pommey S, Eliopoulos N, Galipeau J. Interferon-gamma-stimulated marrow stromal cells: A new type of nonhematopoietic antigen-presenting cell. Blood 2006;107:2570-7.  Back to cited text no. 2
3. Le Blanc K, Ringdén O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 2007;262:509-25.  Back to cited text no. 3
4. Kang JW, Kang KS, Koo HC, Park JR, Choi EW, Park YH. Soluble factors-mediated immunomodulatory effects of canine adipose tissue-derived mesenchymal stem cells. Stem Cells Dev 2008;17:681-93.  Back to cited text no. 4
5. Augello A, Tasso R, Negrini SM, Amateis A, Indiveri F, Cancedda R, et al. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol 2005;35:1482-90.  Back to cited text no. 5
6. Rasmusson I. Immune modulation by mesenchymal stem cells. Exp Cell Res 2006;312:2169-79.  Back to cited text no. 6
7. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006;24:386-98.  Back to cited text no. 7
8. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007;25:2739-49.  Back to cited text no. 8
9. Patel SA, Sherman L, Munoz J, Rameshwar P. Immunological properties of mesenchymal stem cells and clinical implications. Arch Immunol Ther Exp (Warsz) 2008;56:1-8.  Back to cited text no. 9
10. Li C, Zhang W, Jiang X, Mao N. Human-placenta-derived mesenchymal stem cells inhibit proliferation and function of allogeneic immune cells. Cell Tissue Res 2007;330:437-46.  Back to cited text no. 10
11. van den Berk LC, Figdor CG, Torensma R. Mesenchymal stromal cells: Tissue engineers and immune response modulators. Arch Immunol Ther Exp (Warsz) 2008;56:325-9.  Back to cited text no. 11
12. Kong QF, Sun B, Bai SS, Zhai DX, Wang GY, Liu YM, et al. Administration of bone marrow stromal cells ameliorates experimental autoimmune myasthenia gravis by altering the balance of Th1/Th2/Th17/Treg cell subsets through the secretion of TGF-beta. J Neuroimmunol 2009;207:83-91.  Back to cited text no. 12
13. Brooke G, Rossetti T, Pelekanos R, Ilic N, Murray P, Hancock S, et al. Manufacturing of human placenta-derived mesenchymal stem cells for clinical trials. Br J Haematol 2009;144:571-9.  Back to cited text no. 13
14. Koyama N, Okubo Y, Nakao K, Bessho K. Evaluation of pluripotency in human dental pulp cells. J Oral Maxillofac Surg 2009;67:501-6.  Back to cited text no. 14
15. Arora V, Arora P, Munshi AK. Banking stem cells from human exfoliated deciduous teeth (SHED): Saving for the future. J Clin Pediatr Dent 2009;33:289-94.  Back to cited text no. 15
16. Nourbakhsh N, Soleimani M, Taghipour Z, Karbalaie K, Mousavi SB, Talebi A, et al. Induced in vitro differentiation of neural-like cells from human exfoliated deciduous teeth-derived stem cells. Int J Dev Biol 2011;55:189-95.  Back to cited text no. 16
17. Yamaza T, Kentaro A, Chen C, Liu Y, Shi Y, Gronthos S, et al. Immunomodulatory properties of stem cells from human exfoliated deciduous teeth. Stem Cell Res Ther 2010;1:5.  Back to cited text no. 17
18. Alipour R, Sadeghi F, Hashemi-Beni B, Zarkesh-Esfahani SH, Heydari F, Mousavi SB, et al. Phenotypic characterizations and comparison of adult dental stem cells with adipose-derived stem cells. Int J Prev Med 2010;1:164-71.  Back to cited text no. 18
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19. Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantation. Transplantation 2003;75:389-97.  Back to cited text no. 19
20. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005;105:1815-22.  Back to cited text no. 20
21. Yañez R, Lamana ML, García-Castro J, Colmenero I, Ramírez M, Bueren JA. Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells 2006;24:2582-91.  Back to cited text no. 21
22. DelaRosa O, Lombardo E, Beraza A, Mancheño-Corvo P, Ramirez C, Menta R, et al. Requirement of IFN-gamma-mediated indoleamine 2,3-dioxygenase expression in the modulation of lymphocyte proliferation by human adipose-derived stem cells. Tissue Eng Part A 2009;15:2795-806.  Back to cited text no. 22
23. Wang M, Yang Y, Yang D, Luo F, Liang W, Guo S, et al. The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Immunology 2009;126:220-32.  Back to cited text no. 23
24. Chang CJ, Yen ML, Chen YC, Chien CC, Huang HI, Bai CH, et al. Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-gamma. Stem Cells 2006;24:2466-77.  Back to cited text no. 24
25. Wada N, Menicanin D, Shi S, Bartold PM, Gronthos S. Immunomodulatory properties of human periodontal ligament stem cells. J Cell Physiol 2009;219:667-76.  Back to cited text no. 25
26. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringdén O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 2003;57:11-20.  Back to cited text no. 26
27. Potian JA, Aviv H, Ponzio NM, Harrison JS, Rameshwar P. Veto-like activity of mesenchymal stem cells: Functional discrimination between cellular responses to alloantigens and recall antigens. J Immunol 2003;171:3426-34.  Back to cited text no. 27
28. Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB. Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS One 2010;5:e9016.  Back to cited text no. 28
29. 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-gamma. Blood 2006;107:4817-24.  Back to cited text no. 29
30. Schurgers E, Kelchtermans H, Mitera T, Geboes L, Matthys P. Discrepancy between the in vitro and in vivo effects of murine mesenchymal stem cells on T-cell proliferation and collagen-induced arthritis. Arthritis Res Ther 2010;12:R31.  Back to cited text no. 30
31. Roelen DL, van der Mast BJ, in't Anker PS, Kleijburg C, Eikmans M, van Beelen E, et al. Differential immunomodulatory effects of fetal versus maternal multipotent stromal cells. Hum Immunol 2009;70:16-23.  Back to cited text no. 31
32. Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 2005;105:2214-9.  Back to cited text no. 32
33. Nasef A, Zhang YZ, Mazurier C, Bouchet S, Bensidhoum M, Francois S, et al. Selected Stro-1-enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation. Int J Lab Hematol 2009;31:9-19.  Back to cited text no. 33
34. Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003;101:3722-9.  Back to cited text no. 34
35. Deuse T, Stubbendorff M, Tang-Quan K, Phillips N, Kay MA, Eiermann T, et al. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplant 2011;20:655-67.  Back to cited text no. 35
36. Wang L, Lu XF, Lu YR, Liu J, Gao K, Zeng YZ, et al. Immunogenicity and immune modulation of osteogenic differentiated mesenchymal stem cells from Banna minipig inbred line. Transplant Proc 2006;38:2267-9.  Back to cited text no. 36
37. 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;84:231-7.  Back to cited text no. 37
38. Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, et al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 2007;109:228-34.  Back to cited text no. 38
39. Yang SH, Park MJ, Yoon IH, Kim SY, Hong SH, Shin JY, et al. Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10. Exp Mol Med 2009;41:315-24.  Back to cited text no. 39
40. Puissant B, Barreau C, Bourin P, Clavel C, Corre J, Bousquet C, et al. Immunomodulatory effect of human adipose tissue-derived adult stem cells: Comparison with bone marrow mesenchymal stem cells. Br J Haematol 2005;129:118-29.  Back to cited text no. 40
41. Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 6 th ed. Philadelphia: Saunders Elsevier; 2010.  Back to cited text no. 41