Skip to main content

Advertisement

SpringerLink
Log in

Dental pulp stem cells suppress the proliferation of lymphocytes via transforming growth factor-β1

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Dental pulp stem cells (DPSCs) possess self-renewal capability, multi-lineage differentiation potential, and can generate a dentin-pulp-like tissue in vivo, which is promising for tooth regeneration. To enlarge the cells resource of DPSCs and explore the feasibility of DPSCs-mediated immune therapy, it is prerequisite to investigate the immunological properties of DPSCs and the underlying mechanisms. Human DPSCs and peripheral blood mononuclear cells were isolated and cultured. Then we used lymphocytes proliferation assays, cytokines detection, Transwell cultures, neutralization experiments, and flow cytometry to examine the in vitro immune characteristics of DPSCs. We found that DPSCs failed to stimulate allogeneic T cells proliferation and suppressed T cells proliferation, B cells proliferation, and mixed lymphocyte reaction. In addition, DPSCs could up-regulate IL-10, down-regulate the production of IL-2, IL-17, and IFN-γ, and did not affect the production of IL-6. Monoclonal antibody against transforming growth factor-β1 restored the T cells proliferation inhibited by DPSCs. Moreover, the population of regulatory T cells increased significantly and T-helper 17 cells decreased significantly in peripheral blood mononuclear cells co-cultured with DPSCs. These data confirmed that DPSCs are low immunogenic, could inhibit the proliferation of lymphocytes, regulate the production of cytokines in vitro, and the secretion of transforming growth factor-β1 may be involved in this event.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

BMSCs:

Bone marrow mesenchymal stem cells

DPSCs:

Dental pulp stem cells

ELISA:

Enzyme-linked immunosorbent assays

IDO:

Indoleamine 2,3-dioxygenase

IFN-γ:

Interferon γ

iNOS:

Inducible nitric oxide synthase

l-NAME:

N-nitro-l-arginine methyl ester

MLR:

Mixed lymphocyte reaction

MSCs:

Mesenchymal stem cells

1-MT:

1-Methyl-l-tryptophan

PBMCs:

Peripheral blood mononuclear cells

PDLSCs:

Periodontal ligament stem cells

PGE2:

Prostaglandin E2

PHA:

Phytohemagglutinin

SI:

Stimulation index

TGF-β1:

Transforming growth factor-β1

Th17:

T-helper 17

Tregs:

Regulatory T cells

References

  1. Liu Y, Wang S, Shi S. The role of recipient T cells in mesenchymal stem cell-based tissue regeneration. Int J Biochem Cell Biol. 2012;44:2044–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Janjanin S, Djouad F, Shanti RM, Baksh D, et al. Human palatine tonsil: a new potential tissue source of multipotent mesenchymal progenitor cells. Arthritis Res Ther. 2008;10:R83.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Gronthos S, Mankani M, Brahim J, et al. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA. 2000;97:13625–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Gronthos S, Brahim J, Li W, et al. Stem cell properties of human dental pulp stem cells. J Dent Res. 2002;81:531–5.

    Article  CAS  PubMed  Google Scholar 

  5. Gandia C, Armiñan A, García-Verdugo JM, et al. Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction. Stem Cells. 2008;26:638–45.

    Article  PubMed  Google Scholar 

  6. Govindasamy V, Ronald VS, Abdullah AN, et al. Differentiation of dental pulp stem cells into islet-like aggregates. J Dent Res. 2011;90:646–52.

    Article  CAS  PubMed  Google Scholar 

  7. Nesti C, Pardini C, Barachini S, et al. Human dental pulp stem cells protect mouse dopaminergic neurons against MPP+ or rotenone. Brain Res. 2011;1367:94–102.

    Article  CAS  PubMed  Google Scholar 

  8. Wei F, Song T, Ding G, et al. Functional tooth restoration by allogeneic mesenchymal stem cell-based bio-root regeneration in swine. Stem Cells Dev. 2013;22:1752–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Ding G, Liu Y, An Y, et al. Suppression of T cell proliferation by root apical papilla stem cells in vitro. Cells Tissues Organs. 2010;191:357–64.

    Article  PubMed  Google Scholar 

  10. Seo BM, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 2004;364:149–55.

    Article  CAS  PubMed  Google Scholar 

  11. Kortesidis A, Zannettino A, Isenmann S, et al. Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood. 2005;105:3793–801.

    Article  CAS  PubMed  Google Scholar 

  12. Liu O, Xu J, Ding G, et al. Periodontal ligament stem cells regulate B lymphocyte function via programmed cell death protein 1. Stem Cells. 2013;31:1371–82.

    Article  CAS  PubMed  Google Scholar 

  13. Wada N, Menicanin D, Shi S, et al. Immunomodulatory properties of human periodontal ligament stem cells. J Cell Physiol. 2009;219:667–76.

    Article  CAS  PubMed  Google Scholar 

  14. Yañez R, Lamana ML, García-Castro J, et al. 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.

    Article  PubMed  Google Scholar 

  15. Tang R, Wei F, Wei L, et al. Osteogenic differentiated periodontal ligament stem cells maintain their immunomodulatory capacity. J Tissue Eng Regen Med. 2014;8:226–32.

    Article  CAS  PubMed  Google Scholar 

  16. Ding G, Liu Y, Wang W, et al. Allogeneic periodontal ligament stem cell therapy for periodontitis in swine. Stem Cells. 2010;28:1829–38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Yamaza T, Kentaro A, Chen C, et al. Immunomodulatory properties of stem cells from human exfoliated deciduous teeth. Stem Cell Res Ther. 2010;1:5.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Liu D, Xu J, Liu O, et al. Mesenchymal stem cells derived from inflamed periodontal ligaments exhibit impaired immunomodulation. J Clin Periodontol. 2012;39:1174–82.

    Article  CAS  PubMed  Google Scholar 

  19. Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110:3499–506.

    Article  CAS  PubMed  Google Scholar 

  20. Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–86.

    Article  PubMed  Google Scholar 

  21. Sun L, Akiyama K, Zhang H, et al. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells. 2009;27:1421–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Pierdomenico L, Bonsi L, Calvitti M, et al. Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp. Transplantation. 2005;80:836–42.

    Article  PubMed  Google Scholar 

  23. Djouad F, Jackson WM, Bobick BE, et al. Activin A expression regulates multipotency of mesenchymal progenitor cells. Stem Cell Res Ther. 2010;1:11.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Zhao Y, Wang L, Jin Y, et al. Fas ligand regulates the immunomodulatory properties of dental pulp stem cells. J Dent Res. 2012;91:948–54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815–22.

    Article  CAS  PubMed  Google Scholar 

  26. Akiyama K, Chen C, Wang D, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell. 2012;10:544–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Holan V, Pokorna K, Prochazkova J, et al. Immunoregulatory properties of mouse limbal stem cells. J Immunol. 2010;184:2124–9.

    Article  CAS  PubMed  Google Scholar 

  28. Atoui R, Chiu RC. Concise review: immunomodulatory properties of mesenchymal stem cells in cellular transplantation: update, controversies, and unknowns. Stem Cells Transl Med. 2012;1:200–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Luz-Crawford P, Kurte M, Bravo-Alegría J, et al. Mesenchymal stem cells generate a CD4+CD25+Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther. 2013;4:65.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Potian JA, Aviv H, Ponzio NM, et al. Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. J Immunol. 2003;171:3426–34.

    Article  CAS  PubMed  Google Scholar 

  31. Beyth S, Borovsky Z, Mevorach D, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood. 2005;105:2214–9.

    Article  CAS  PubMed  Google Scholar 

  32. Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838–43.

    Article  PubMed  Google Scholar 

  33. Meisel R, Zibert A, Laryea M, et al. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103:4619–21.

    Article  CAS  PubMed  Google Scholar 

  34. Sato K, Ozaki K, Oh I, et al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. 2007;109:228–34.

    Article  CAS  PubMed  Google Scholar 

  35. Kikuiri T, Kim I, Yamaza T, et al. Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw-like disease in mice. J Bone Miner Res. 2010;25:1668–79.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.

    Article  CAS  PubMed  Google Scholar 

  37. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol. 2008;9:239–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Garrett-Sinha LA, John S, Gaffen SL. IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol. 2008;20:519–25.

    Article  CAS  PubMed  Google Scholar 

  39. La Cava A. T-regulatory cells in systemic lupus erythematosus. Lupus. 2008;17:421–5.

    Article  PubMed  Google Scholar 

  40. Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003;198:1875–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Hori S, Takahashi T, Sakaguchi S. Control of autoimmunity by naturally arising regulatory CD4+ T cells. Adv Immunol. 2003;81:331–71.

    Article  CAS  PubMed  Google Scholar 

  42. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531–62.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China (No. 81070799 to G.D., and No. 81222011 to Y.L.), the Excellent Young Researchers Foundation of Shandong Province (No. BS2010SW033 to G.D.), and Science and Technology Activities of Beijing Overseas Students Preferred Foundation (to Y.L.).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Stomatology, Yidu Central Hospital, Weifang Medical University, Linglongshan South Road No. 4138, Qingzhou, 262500, Shandong, People’s Republic of China

    Gang Ding & Jianyi Niu

  2. Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory for Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, 100069, China

    Yi Liu

Authors
  1. Gang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianyi Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gang Ding.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, G., Niu, J. & Liu, Y. Dental pulp stem cells suppress the proliferation of lymphocytes via transforming growth factor-β1. Human Cell 28, 81–90 (2015). https://doi.org/10.1007/s13577-014-0106-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-014-0106-y

Keywords

Search

Navigation