Functional tooth restoration by allogeneic mesenchymal stem cell-based bio-root regeneration in swine.
Our previous proof-of-concept study showed the feasibility of regenerating the dental stem cell-based bioengineered tooth root (bio-root) structure in a large animal model. Here, we used allogeneic dental mesenchymal stem cells to regenerate bio-root, and then installed a crown on the bio-root to restore tooth function. A root shape hydroxyapatite tricalcium phosphate scaffold containing dental pulp stem cells was covered by a Vc-induced periodontal ligament stem cell sheet and implanted into a newly generated jaw bone implant socket. Six months after implantation, a prefabricated porcelain crown was cemented to the implant and subjected to tooth function. Clinical, radiological, histological, ultrastructural, systemic immunological evaluations and mechanical properties were analyzed for dynamic changes in the bio-root structure. The regenerated bio-root exhibited characteristics of a normal tooth after 6 months of use, including dentinal tubule-like and functional periodontal ligament-like structures. No immunological response to the bio-roots was observed. We developed a standard stem cell procedure for bio-root regeneration to restore adult tooth function. This study is the first to successfully regenerate a functional bio-root structure for artificial crown restoration by using allogeneic dental stem cells and Vc-induced cell sheet, and assess the recipient immune response in a preclinical model.
Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China.
Fulan
F
Wei
Tieli
T
Song
Gang
G
Ding
Junji
J
Xu
Yi
Y
Liu
Dayong
D
Liu
Zhipeng
Z
Fan
Chunmei
C
Zhang
Songtao
S
Shi
Songlin
S
Wang
D000818:Animals; D003442:Crowns; D003782:Dental Pulp / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D003804:Dentin / Q000502:physiology; D006882:Hydroxyapatites / Q000378:metabolism; D008422:Materials Testing; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D010513:Periodontal Ligament / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D020127:Recovery of Function; D012038:Regeneration / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014092:Tooth Root / Q000502:physiology* / Q000601:surgery; D014184:Transplantation, Homologous
D006882:Hydroxyapatites; C074950:hydroxyapatite-beta tricalcium phosphate