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Yonsei Med J. 2017 Sep;58(5):1031-1039. doi: 10.3349/ymj.2017.58.5.1031.

Immune Tolerance of Human Dental Pulp-Derived Mesenchymal Stem Cells Mediated by CD4⁺CD25⁺FoxP3⁺ Regulatory T-Cells and Induced by TGF-β1 and IL-10.

Hong JW1,2, Lim JH1,3, Chung CJ4, Kang TJ1,5, Kim TY4, Kim YS1,3, Roh TS1,3, Lew DH1,3.

Author information

1
Department of Plastic & Reconstructive Surgery, College of Medicine, Yonsei University, Seoul, Korea.
2
Institute for Human Tissue Restoration, College of Medicine, Yonsei University, Seoul, Korea. hsaturn@hanmail.net.
3
Institute for Human Tissue Restoration, College of Medicine, Yonsei University, Seoul, Korea.
4
Department of Orthodontics, College of Dentistry, Yonsei University, Seoul, Korea.
5
Yujin Plastic Surgery, Seoul, Korea.

Abstract

PURPOSE:

Most studies on immune tolerance of mesenchymal stem cells (MSCs) have been performed using MSCs derived from bone marrow, cord blood, or adipose tissue. MSCs also exist in the craniofacial area, specifically in teeth. The purpose of this study was to evaluate the mechanisms of immune tolerance of dental pulp-derived MSC (DP-MSC) in vitro and in vivo.

MATERIALS AND METHODS:

We isolated DP-MSCs from human dental pulp and co-cultured them with CD4⁺ T-cells. To evaluate the role of cytokines, we blocked TGF-β and IL-10, separately and together, in co-cultured DP-MSCs and CD4⁺ T-cells. We analyzed CD25 and FoxP3 to identify regulatory T-cells (Tregs) by fluorescence-activated cell sorting (FACS) and real-time PCR. We performed alloskin grafts with and without DP-MSC injection in mice. We performed mixed lymphocyte reactions (MLRs) to check immune tolerance.

RESULTS:

Co-culture of CD4⁺ T-cells with DP-MSCs increased the number of CD4⁺CD25⁺FoxP3⁺ Tregs (p<0.01). TGF-β or/and IL-10 blocking suppressed Treg induction in co-cultured cells (p<0.05). TGF-β1 mRNA levels were higher in co-cultured DP-MSCs and in co-cultured CD4⁺ T-cells than in the respective monocultured cells. However, IL-10 mRNA levels were not different. There was no difference in alloskin graft survival rate and area between the DP-MSC injection group and the non-injection group. Nonetheless, MLR was reduced in the DP-MSC injected group (p<0.05).

CONCLUSION:

DP-MSCs can modulate immune tolerance by increasing CD4⁺CD25⁺FoxP3⁺ Tregs. TGF-β1 and IL-10 are factors in the immune-tolerance mechanism. Pure DP-MSC therapy may not be an effective treatment for rejection, although it may module immune tolerance in vivo.

KEYWORDS:

Dental pulp; immune tolerance; mesenchymal stem cell

PMID:
28792150
PMCID:
PMC5552631
DOI:
10.3349/ymj.2017.58.5.1031
[Indexed for MEDLINE]
Free PMC Article

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