title: Differentiation of mouse embryonic stem cells into dental epithelial-like cells induced by ameloblasts serum-free conditioned medium.
abstract: Embryonic stem cells (ESCs) possess an intrinsic self-renewal ability and can differentiate into numerous types of functional tissue cells; however, whether ESCs can differentiate toward the odontogenic lineage is still unknown. In this study, we developed an efficient culture strategy to induce the differentiation of murine ESCs (mESCs) into dental epithelial cells. By culturing mESCs in ameloblasts serum-free conditioned medium (ASF-CM), we could induce their differentiation toward dental epithelial cell lineages; however, similar experiments with the tooth germ cell-conditioned medium (TGC-CM) did not yield effective results. After culturing the cells for 14days in the differentiation-inducing media, the expression of ameloblast-specific proteins such as cytokeratin (CK)14, ameloblastin (AMBN), and amelogenin (AMGN) was markedly higher in mESCs obtained with embryoid body (EB) formation than in mESCs obtained without EB formation. We observed that immunocompromised mice implanted with induced murine EBs (mEBs) showed tissue regenerative capacity and produced odontogenic epithelial-like structures, whereas those implanted with mSCE monolayer cells mainly formed connective tissues. Thus, for the first time, we report that ASF-CM provides a suitable microenvironment for inducing mESC differentiation along the odontogenic epithelial cell lineage. This result has important implications for tooth tissue engineering.
authors.affiliation: Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, 710032 Shaanxi, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ning
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Guo
authors.forename: Juan
authors.initials: J
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.forename: Yinzhong
authors.initials: Y
authors.lastname: Duan
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000565:Ameloblasts / Q000378:metabolism*; D053523:Amelogenin / Q000096:biosynthesis; D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000378:metabolism / Q000494:pharmacology; D003746:Dental Enamel Proteins / Q000096:biosynthesis; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology; D053547:Keratin-14 / Q000096:biosynthesis; D051379:Mice; D009805:Odontogenesis; D023822:Tissue Engineering / Q000379:methods*; D014070:Tooth / Q000166:cytology / Q000254:growth & development*
chemical_list: C490890:Ambn protein, mouse; D053523:Amelogenin; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D003746:Dental Enamel Proteins; D053547:Keratin-14