Dental Stem Cells-Based Tissue Regeneration in a Large Animal Model (Pages: 0-0)

Yi Liu *, Songlin Wang , Songtao Shi , Ying Zheng , Dianji Fang , George T.J. Huang , Chunmei Zhang ,


Objective: The dental tissues contain a variety of stem cells, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from the apical papilla (SCAP). These dental tissues-related stem cells possess high proliferation and differentiation capacities, and can be acquired easily from useless teeth, such as exfoliated deciduous teeth (SHED), extracted impacted third molars or orthodontic extracted teeth (DPSCs, PDLSCs and SCAP). The purpose of our studies is to perform oral and craniofacial tissue regeneration using these dental tissues-related mesenchymal stem cells at pre-clinical level in a large animal model (swine). Materials and Methods: Dental related stem cells were obtained from extracted teeth of the miniature pigs and then expanded ex vivo to enrich cell numbers. The characteristics and differentiation abilities of these stem cells were analyzed. Then, we utilized these stem cells to treat created periodontal lesions, to regenerate bioroots and to repair critical size bone defects in miniature pigs. (1) A typical periodontitis animal model was developed on miniature pig’s first molar. PDLSCs were utilized to treat periodontal defect lesion and regenerate the new periodontal tissues. (2) Using a minipig model, autologous SCAP and PDLSCs were loaded onto HA/TCP and gelfoam scaffolds, respectively, and implanted into sockets of the lower jaw. Three months later, the bioroot was exposed, and a porcelain crown was inserted. (3) Autologous SHED were used to repair critical-size mandibular bone defects in minipig. (4) PDLSCs and bone marrow mesenchymal stem cells (BMMSC) were used to reconstruct orofacial tissues for changing orofacial appearance. Results: Dental tissues related stem cells could be isolated successfully from miniature pig. A subset of these cells retained expression of early-stage markers of stem cells and had the abilities of single colon forming, high proliferation and differentiation. (1) PDLSCs appeared to have an excellent capacity to form bone, cementum, and periodontal ligament. The GFP-labeled cells were present in newly formed periodontal bones and had differentiated to osteoblasts, suggesting that transplanted PDLSCs had contributed to periodontal tissue regeneration in vivo, leading to a favorable treatment for periodontitis. (2) The structures of bioroot developed by SCAP and PDLSCs were still different from a natural root in a random manner. Nevertheless, the bioroot was encircled with periodontal ligament tissue and appears to have a natural relationship with the surrounding bone, and the mechanical strength of bioroot was about 70% of normal tooth root. Although there were many challenges, the approach was relatively a quick way of creating a root onto which an artificial crown could be installed. (3) SHED (SPDs) were capable of regenerating critical-size defects in the orofacial bone, and might potentially serve as an alternative stem-cell-based approach in the reconstruction of alveolar and orofacial bone defects. (4) BMMSCs could change the orofacial appearance by extending body bone tissues in minipig and subcutaneous transplantation of PDLSCs could form substantial amounts of collagen fibers and improve facial wrinkles in mouse. Conclusion: These studies demonstrate dental tissues-related stem cells are hidden treasures and provide promising potential application for tissue engineering to oral and craniofacial plastic surgery and diseases therapy.