There is a great demand thefor the repair of craniofacial bone defects. Despite the recent studies suggest that mesenchymal stem deciduous teeth (MSC) could be used to repair cranial defects in animal models, autologous grafts from axial and appendicular bones commonly used to repair orofacial bone defects often result in an unfavorable outcome. Bridging orofacial defects with grafts obtained from an orofacial donor site are usually more successful than those from non-orofacial sites, indicating that anatomic skeletal site-specific differences affect graft integration. Stem cells from Human Exfoliated Deciduous teeth (SHED) possess MSC characteristics and show extremely high proliferation capacity, suggesting that culture expanded small number of SHED can provide sufficient number of cells for clinical use. Therefore, SHED would be an appropriate accessible stem cell resource for repairing neural crest-related orofacial bone defects. Our preliminary data showed that regenerative and immunomodulatory properties of SHED are regulated by telomerase activity. Therefore, our hypothesis is that SHED-based tissue regeneration can be significantly improved with understanding mechanism by which telomerase regulates osteogenic differentiation and immunomodulation of SHED. In this application, we will characterize the mechanism by which activation of telomerase activity improves SHED-mediated bone regeneration for repairing calvarial defects. On the basis of our novel findings that telomerase governs immunomodulatory function of SHED, we will examine how telomerase controls SHED-mediated immune regulation. Finally, we will link recipient immunoregulation to SHED-based tissue regeneration. Collectively, novel findings from our proposed studies will provide a molecular basis for understanding SHED-based therapies. Significance: These studies will most likely lead to: 1) unveiling novel molecular mechanisms by which telomerase associated pathways govern osteogenesis and immunomodulation of SHED;and 2) developing new therapeutic strategies to break through the critical barrier for improving calvarial bone regeneration via regulation of recipient T cells.

Public Health Relevance

This study seeks to improve mesenchymal stem cell (SHED)-based regenerative therapy for repairing calvarial defects and improve mesenchymal stem cell (SHED)-based tissue regeneration via regulation of recipient T cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE017449-07
Application #
8658421
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Lumelsky, Nadya L
Project Start
2006-04-01
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
7
Fiscal Year
2014
Total Cost
$410,938
Indirect Cost
$160,938
Name
University of Southern California
Department
Dentistry
Type
Schools of Dentistry
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Moshaverinia, Alireza; Chen, Chider; Xu, Xingtian et al. (2014) Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold. Tissue Eng Part A 20:611-21
Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider et al. (2014) Application of stem cells derived from the periodontal ligament or gingival tissue sources for tendon tissue regeneration. Biomaterials 35:2642-50
Liu, Y; Wang, L; Liu, S et al. (2014) Transplantation of SHED prevents bone loss in the early phase of ovariectomy-induced osteoporosis. J Dent Res 93:1124-32
Chen, Chider; Akiyama, Kentaro; Yamaza, Takayoshi et al. (2014) Telomerase governs immunomodulatory properties of mesenchymal stem cells by regulating FAS ligand expression. EMBO Mol Med 6:322-34
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Yang, Ruili; Liu, Yi; Kelk, Peyman et al. (2013) A subset of IL-17(+) mesenchymal stem cells possesses anti-Candida albicans effect. Cell Res 23:107-21
Xu, X; Chen, C; Akiyama, K et al. (2013) Gingivae contain neural-crest- and mesoderm-derived mesenchymal stem cells. J Dent Res 92:825-32
Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider et al. (2013) Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration. Acta Biomater 9:9343-50
Qin, Haiyan; Qu, Cunye; Yamaza, Takayoshi et al. (2013) Ossifying fibroma tumor stem cells are maintained by epigenetic regulation of a TSP1/TGF-*/SMAD3 autocrine loop. Cell Stem Cell 13:577-89

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