Induction of human keratinocytes into enamel-secreting ameloblasts.
Mammalian tooth development relies heavily on the reciprocal and sequential interactions between cranial neural crest-derived mesenchymal cells and stomadial epithelium. During mouse tooth development, odontogenic potential, that is, the capability to direct an adjacent tissue to form a tooth, resides in dental epithelium initially, and shifts subsequently to dental mesenchyme. Recent studies have shown that mouse embryonic dental epithelium possessing odontogenic potential is able to induce the formation of a bioengineered tooth crown when confronted with postnatal mesenchymal stem cells of various sources. Despite many attempts, however, postnatal stem cells have not been used successfully as the epithelial component in the generation of a bioengineered tooth. We show here that epithelial sheets of cultured human keratinocytes, when recombined with mouse embryonic dental mesenchyme, are able to support tooth formation. Most significantly, human keratinocytes, recombined with mouse embryonic dental mesenchyme in the presence of exogenous FGF8, are induced to express the dental epithelial marker PITX2 and differentiate into enamel-secreting ameloblasts that develop a human-mouse chimeric whole tooth crown. We conclude that in the presence of appropriate odontogenic signals, human keratinocytes can be induced to become odontogenic competent; and that these are capable of participating in tooth crown morphogenesis and differentiating into ameloblasts. Our studies identify human keratinocytes as a potential cell source for in vitro generation of bioengineered teeth that may be used in replacement therapy.
Wang
Bingmei
B
Fujian Key Laboratory of Developmental and Neuro Biology, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian Province, PR China.
Li
Liwen
L
Du
Shengrong
S
Liu
Chao
C
Lin
Xin
X
Chen
YiPing
Y
Zhang
Yanding
Y
D000565:Ameloblasts / Q000378:metabolism; D000818:Animals; D057005:Bioengineering; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D003743:Dental Enamel / Q000378:metabolism; D004848:Epithelium / Q000196:embryology; D051524:Fibroblast Growth Factor 8; D006801:Humans; D015603:Keratinocytes; D008297:Male; D008648:Mesoderm; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D009805:Odontogenesis; D015398:Signal Transduction; D013234:Stem Cells; D014070:Tooth / Q000196:embryology*; D019228:Tooth Crown
C496456:FGF8 protein, human; D051524:Fibroblast Growth Factor 8