Immunomodulatory properties of stem cells from human exfoliated deciduous teeth.
BACKGROUND
Stem cells from human exfoliated deciduous teeth (SHED) have been identified as a population of postnatal stem cells capable of differentiating into osteogenic and odontogenic cells, adipogenic cells, and neural cells. Herein we have characterized mesenchymal stem cell properties of SHED in comparison to human bone marrow mesenchymal stem cells (BMMSCs).


METHODS
We used in vitro stem cell analysis approaches, including flow cytometry, inductive differentiation, telomerase activity, and Western blot analysis to assess multipotent differentiation of SHED and in vivo implantation to assess tissue regeneration of SHED. In addition, we utilized systemic SHED transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice.


RESULTS
We found that SHED are capable of differentiating into osteogenic and adipogenic cells, expressing mesenchymal surface molecules (STRO-1, CD146, SSEA4, CD73, CD105, and CD166), and activating multiple signaling pathways, including TGFbeta, ERK, Akt, Wnt, and PDGF. Recently, BMMSCs were shown to possess an immunomodulatory function that leads to successful therapies for immune diseases. We examined the immunomodulatory properties of SHED in comparison to BMMSCs and found that SHED had significant effects on inhibiting T helper 17 (Th17) cells in vitro. Moreover, we found that SHED transplantation is capable of effectively reversing SLE-associated disorders in MRL/lpr mice. At the cellular level, SHED transplantation elevated the ratio of regulatory T cells (Tregs) via Th17 cells.


CONCLUSIONS
These data suggest that SHED are an accessible and feasible mesenchymal stem cell source for treating immune disorders like SLE.
Yamaza
Takayoshi
T
Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA. yamazata@dent.kyushu-u.ac.jp
Kentaro
Akiyama
A
Chen
Chider
C
Liu
Yi
Y
Shi
Yufang
Y
Gronthos
Stan
S
Wang
Songlin
S
Shi
Songtao
S
D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells; D049109:Cell Proliferation; D005260:Female; D064593:Heterografts; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D018655:Lymphocyte Count; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008819:Mice, Nude; D055495:Neurogenesis / Q000502:physiology; D009805:Odontogenesis / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D012038:Regeneration; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D019098:Telomerase / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*; D014094:Tooth, Deciduous / Q000166:cytology
D019098:Telomerase