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.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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. 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. 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). DP-

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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