title: Tooth root regeneration using dental follicle cell sheets in combination with a dentin matrix - based scaffold.
abstract: Stem cell mediated tissue engineering has been acknowledged as a prospective strategy for repairing and replacing damaged and lost tissues. However, the low survival rate of implanted stem cells proves to be a major challenge in the management of transplantation failures. While previous studies have indicated the effectiveness of tissue engineered cell sheets in improving the survival rate of implanted cells, we have recently demonstrated the use of treated dentin matrix (TDM) as a biological scaffold and dental follicle cells (DFCs) as the seeding cells for dentinogenesis and tooth root construction. This study proposes a strategy utilizing TDM with human dental follicle cell sheets (DFCSs) for root regeneration. The biological characteristics and changes of human DFCSs under the effect of TDM were studied with scanning electron microscopy, transmission electron microscopy, immunofluorescence microscopy, immunohistochemistry and quantitative real-time PCR. DFCSs combined with TDM were implanted subcutaneously into the dorsum of mice. Histological examination of the harvested grafts revealed a whirlpool-like alignment of the DFCs in multiple layers that were positive for COLI, integrinβ1, fibronectin and alkaline phosphatase (ALP), suggestive of the formation of a rich extracellular matrix. DFCSs, under the effect of TDM, highly expressed DMP-1 and bone sialoprotein (BSP), indicating their potential for odontogenesis and osteogenesis. Importantly, in vivo, TDM could induce and support DFCSs to develop new dentin-pulp like tissues and cementum-periodontal complexes that were positive for markers such as DSP, nestin and VIII factors, COLI and cementum attachment protein (CAP), implying successful root regeneration. Therefore, DFCSs combined with TDM may prove to be a better strategy for the construction of tooth root, and is a prospective approach that could be utilized for the treatment of root or tooth defect or loss in future.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Zou
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Long
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Weihua
authors.initials: W
authors.lastname: Guo
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003795:Dental Sac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003804:Dentin / Q000378:metabolism*; D017886:Durapatite / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D051379:Mice; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014092:Tooth Root / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D002130:Calcium Phosphates; D017886:Durapatite; C018392:tricalcium phosphate