TY - JOUR
T1 - Immune therapeutic potential of stem cells from human supernumerary teeth
AU - Makino, Y.
AU - Yamaza, H.
AU - Akiyama, K.
AU - Ma, L.
AU - Hoshino, Y.
AU - Nonaka, K.
AU - Terada, Y.
AU - Kukita, T.
AU - Shi, S.
AU - Yamaza, T.
N1 - Funding Information:
This work was supported by grants-in-aid for Scientific Research (B) (No. 25293405 to TY), Scientific Research (B) (No. 25463187 to HY), Challenging Exploratory Research Project (No. 24659815 to TY), and Young Scientists (B) (No. 20790260 to H.Y.) from the Japan Society for Promotion of Science and by grants from the National Institute of Dental and Craniofacial Research, National Institutes of Health, US Department of Health and Human Services ( R01DE17449 and R01DE019156 to S.S.). We are grateful to Dr. Keiji Masuda (Department of Pediatric Dentistry, Kyushu University Hospital) for his clinical support.
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
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U2 - 10.1177/0022034513490732
DO - 10.1177/0022034513490732
M3 - Article
C2 - 23697344
AN - SCOPUS:84879150884
SN - 0022-0345
VL - 92
SP - 609
EP - 615
JO - Journal of Dental Research
JF - Journal of Dental Research
IS - 7
ER -