Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Higashi-ku, Fukuoka, Japan.
J Dent Res. 2013 Jul;92(7):609-15. doi: 10.1177/0022034513490732. Epub 2013 May 22.
Discoveries of immunomodulatory functions in mesenchymal stem cells (MSCs) have suggested that they might have therapeutic utility in treating immune diseases. Recently, a novel MSC population was identified from dental pulp of human supernumerary teeth, and its multipotency characterized. Herein, we first examined the in vitro and in vivo immunomodulatory functions of human supernumerary tooth-derived stem cells (SNTSCs). SNTSCs suppressed not only the viability of T-cells, but also the differentiation of interleukin 17 (IL-17)-secreting helper T (Th17)-cells in in vitro co-culture experiments. In addition, systemic SNTSC transplantation ameliorated the shortened lifespan and elevated serum autoantibodies and nephritis-like renal dysfunction in systemic lupus erythematosus (SLE) model MRL/lpr mice. SNTSC transplantation also suppressed in vivo increased levels of peripheral Th17 cells and IL-17, as well as ex vivo differentiation of Th17 cells in MRL/lpr mice. Adoptive transfer experiments demonstrated that SNTSC-transplanted MRL/lpr mouse-derived T-cell-adopted immunocompromised mice showed a longer lifespan in comparison with non-transplanted MRL/lpr mouse-derived T-cell-adopted immunocompromised mice, indicating that SNTSC transplantation suppresses the hyper-immune condition of MRL/lpr mice through suppressing T-cells. Analysis of these data suggests that SNTSCs are a promising MSC source for cell-based therapy for immune diseases such as SLE.
间充质干细胞 (MSCs) 的免疫调节功能的发现表明,它们可能在治疗免疫性疾病方面具有治疗作用。最近,从人类多生牙牙髓中鉴定出一种新型 MSC 群体,并对其多能性进行了表征。在此,我们首次研究了人多生牙源性干细胞 (SNTSCs) 的体外和体内免疫调节功能。SNTSCs 不仅抑制 T 细胞的活力,而且在体外共培养实验中抑制白细胞介素 17 (IL-17) 分泌辅助性 T (Th17) 细胞的分化。此外,全身性 SNTSC 移植改善了红斑狼疮 (SLE) 模型 MRL/lpr 小鼠的寿命缩短、血清自身抗体升高和肾炎样肾功能障碍。SNTSC 移植还抑制了 MRL/lpr 小鼠体内外周 Th17 细胞和 IL-17 的增加水平,以及体外 MRL/lpr 小鼠 Th17 细胞的分化。过继转移实验表明,与未移植 MRL/lpr 小鼠来源的 T 细胞过继免疫受损小鼠相比,接受 SNTSC 移植的 MRL/lpr 小鼠来源的 T 细胞过继免疫受损小鼠的寿命更长,表明 SNTSC 移植通过抑制 T 细胞抑制 MRL/lpr 小鼠的高免疫状态。这些数据分析表明,SNTSCs 是用于治疗 SLE 等免疫性疾病的细胞治疗有前途的 MSC 来源。