Immune Therapeutic Potential of Stem Cells from Human Supernumerary Teeth

Abstract

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.