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.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Skeletal Biology Development and Disease Study Section (SBDD)
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Lumelsky, Nadya L
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University of Southern California
Schools of Dentistry
Los Angeles
United States
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Chen, Chider; Wang, Dandan; Moshaverinia, Alireza et al. (2017) Mesenchymal stem cell transplantation in tight-skin mice identifies miR-151-5p as a therapeutic target for systemic sclerosis. Cell Res 27:559-577
Liu, S; Jin, Y; Shi, S (2017) Autophagy guarantees stemness of muscle stem cells by maintaining quiescence. Oral Dis 23:139-140
Ansari, Sahar; Chen, Chider; Xu, Xingtian et al. (2016) Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors. Ann Biomed Eng 44:1908-20
Yang, R; Liu, Y; Shi, S (2016) Hydrogen Sulfide Regulates Homeostasis of Mesenchymal Stem Cells and Regulatory T Cells. J Dent Res 95:1445-1451
Gu, Yongchun; Shi, Songtao (2016) Transplantation of gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis. Arthritis Res Ther 18:262
Chen, Fa-Ming; Gao, Li-Na; Tian, Bei-Min et al. (2016) Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial. Stem Cell Res Ther 7:33
Diniz, Ivana M A; Chen, Chider; Ansari, Sahar et al. (2016) Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD-Coupled Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for Peri-Implantitis. J Prosthodont 25:105-15
Chen, Chih-Chiang; Wang, Lei; Plikus, Maksim V et al. (2015) Organ-level quorum sensing directs regeneration in hair stem cell populations. Cell 161:277-90
Wang, L; Liu, S; Zhao, Y et al. (2015) Osteoblast-induced osteoclast apoptosis by fas ligand/FAS pathway is required for maintenance of bone mass. Cell Death Differ 22:1654-64
Liu, Yi; Yang, Ruili; Shi, Songtao (2015) Systemic infusion of mesenchymal stem cells improves cell-based bone regeneration via upregulation of regulatory T cells. Tissue Eng Part A 21:498-509

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