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.
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.
|Yang, Ruili; Yu, Tingting; Kou, Xiaoxing et al. (2018) Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter. Nat Commun 9:2143|
|Liu, Yao; Jing, Huan; Kou, Xiaoxing et al. (2018) PD-1 is required to maintain stem cell properties in human dental pulp stem cells. Cell Death Differ 25:1350-1360|
|Kou, Xiaoxing; Xu, Xingtian; Chen, Chider et al. (2018) The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing. Sci Transl Med 10:|
|Liu, Dawei; Kou, Xiaoxing; Chen, Chider et al. (2018) Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors. Cell Res 28:918-933|
|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|
|Gu, Yongchun; Shi, Songtao (2016) Transplantation of gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis. Arthritis Res Ther 18:262|
|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|
|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|
|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|
Showing the most recent 10 out of 61 publications