The induction of enamel and dentin complexes by subcutaneous implantation of reconstructed human and murine tooth germ elements

Abstract

Tooth induction by xenogenic graft of reconstructed human tooth germ components has never been attempted. Here we report our first attempt at a transplantation of human tooth germ components, heterologously recombined with mouse dental epithelia, into immunocompromised animals. Human third molar tooth germs enucleated from young patients as prophylactic treatment for orthodontic reasons were collected. The whole or minced human dental papilla was reconstructed with human- or mouse molar enamel epithelium, and transplanted in the dorsal aspect of C.B-17/Icr-scid Jcl mice. The transplant of human dental papilla reconstructed with human enamel epithelium formed thin dentin and immature enamel layers by 3 to 4 weeks, but remained extremely small in quantity due to a shortage of epithelial components in the graft. The addition of E16 mouse molar enamel organs (n=10-12) to each graft augmented the formation of tooth germ-like structures, but the differentiation of mouse molar ameloblasts was suppressed. However, once a solid layer of mineralized dentin was established, mouse ameloblasts accelerated their differentiation, and completed the enamel matrix formation and maturation within the following 4 weeks, whereas human ameloblasts, which had interacted with human dental papilla, remained in the stage of matrix formation during the same period. These data imply that, in reconstructed transplants, the differentiation of mouse dental epithelia is restrained by putative suppressive factors derived from human dental papilla until they are separated by mineralized dentin layers that serve as a diffusion barrier. The mouse enamel organ nevertheless retains its own phenotypic characteristics and intrinsic timing of cell differentiation and function.

Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model

“…reported that the frequency of tooth germ reconstruction was influenced by critical causes regarding the cell seeding density or insufficient direct contact with epithelial and mesenchymal tooth germ cells44. Furthermore, certain factors, such as distinctive gradual tissue development ( i.e., developmental speed) in large animals, might reduce the generation rate of bioengineered tooth germ during the tissue organization process reconstructed from single cells45. This advancement is significant for the concept of whole-tooth replacement therapy, in which a bioengineered tooth germ can be reconstructed utilizing the bioengineered organ germ method and postnatal stem cells.…”

Regenerative Therapy in Dentistry: A Review

“…It's possible to produce tooth crowns using fully intact or partially dissected tooth germs under suitable environments such as in vivo grafting on chick chorioaltantoic membrane, sub-cutaneous transplants, or ocular or subrenal grafts, or in vitro organ culture [18][19][20]. Both, nutrients, and oxygen are supplied by every implant site to allow the tooth germ differentiation into a mature tooth.…”

Dental Tissue Regeneration – A Mini-Review

“…Early studies showed that it was possible to regenerate tooth crowns from intact or partially dissected tooth germs if suitable environments were provided, such as in vitro organ culture, in vivo grafting on chick chorioallantoic membrane, ocular or subrenal grafts or subcutaneous transplants [46][47][48] . Each of these implant sites provides nutrients and oxygen to nurture tooth germ differentiation into mature teeth.…”