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.
Bibliographical noteFunding Information:
This study was supported by a faculty research grant of Yonsei University College of Medicine for 2012(6-2012-0051) and by funding for Young Investigator research (2014), Korean Society for Transplantation. This study was performed based on previous adipose-derived mesenchymal stem cell research supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(2012R1A1A1010117). We appreciate Prof. Chooryung J. CHUNG, DDS, PhD for providing DP-MSCs and discussion. We also appreciate Dr. Tae Jo, KANG for discussion.
© Yonsei University College of Medicine 2017.
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