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Bioengineering of a human whole tooth: progress and challenge.

Zhang Y, Chen Y - Cell Regen (Lond) (2014)

Bottom Line: A major challenge in stem cell-based bioengineering of an implantable human tooth is to identify appropriate sources of postnatal stem cells that are odontogenic competent as the epithelial component due to the lack of enamel epithelial cells in adult teeth.In a recent issue (2013, 2:6) of Cell Regeneration, Cai and colleagues reported that epithelial sheets derived from human induced pluripotent stem cells (iPSCs) can functionally substitute for tooth germ epithelium to regenerate tooth-like structures, providing an appealing stem cell source for future human tooth regeneration.

View Article: PubMed Central - PubMed

Affiliation: Fujian Key Laboratory of Developmental and Neuro Biology, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian Province P.R. China.

ABSTRACT
A major challenge in stem cell-based bioengineering of an implantable human tooth is to identify appropriate sources of postnatal stem cells that are odontogenic competent as the epithelial component due to the lack of enamel epithelial cells in adult teeth. In a recent issue (2013, 2:6) of Cell Regeneration, Cai and colleagues reported that epithelial sheets derived from human induced pluripotent stem cells (iPSCs) can functionally substitute for tooth germ epithelium to regenerate tooth-like structures, providing an appealing stem cell source for future human tooth regeneration.

No MeSH data available.


Related in: MedlinePlus

A blueprint of stem cell-based tooth regeneration with a scaffold-free approach. Schematic procedures of stem cell-based scaffold-free tooth regeneration in humans. The procedures include induction of iPSCs or epithelial derived stem cells into epithelial (epi.) sheets and induction of iPSCs or dental mesenchymal (mes.) stem cells into mesenchymal masses with odontogenic potential, tissue recombination, in vitro organ culture of the recombinants to the late bud or early cap stage, implantation of bioengineered tooth germs into the lost tooth sites of patients, and regeneration of functional replacement teeth.
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Fig1: A blueprint of stem cell-based tooth regeneration with a scaffold-free approach. Schematic procedures of stem cell-based scaffold-free tooth regeneration in humans. The procedures include induction of iPSCs or epithelial derived stem cells into epithelial (epi.) sheets and induction of iPSCs or dental mesenchymal (mes.) stem cells into mesenchymal masses with odontogenic potential, tissue recombination, in vitro organ culture of the recombinants to the late bud or early cap stage, implantation of bioengineered tooth germs into the lost tooth sites of patients, and regeneration of functional replacement teeth.

Mentions: Certainly, identification of novel adult human stem cell sources is not yet the final solution for tooth regeneration. Based on the characteristic features of tooth development, to generate an implantable tooth germ in vitro, one of the cell sources, either epithelial or mesenchymal population, must acquire odontogenic potential to initiate regenerative process. In fact, despite the fact that human iPSC-derived epithelial cells [21] as well as human keratinocytes [20] and gingival epithelial cells [19] are able to differentiate into enamel-secreting ameloblasts in response to tooth-inducing signals from the mouse embryonic dental mesenchyme, none of these cell populations possess odontogenic potential. In addition, all the human postnatal mesenchymal stem cells of dental origin identified so far, while capable of differentiating into various types of dental tissues, do not have tooth-inducing capability. Thus conferring cells with odontogenic potential is a major challenge. It is well established that epithelial-mesenchymal interactions are mediated by growth factors, and many growth factors are repeatedly utilized at different stages of tooth development [15]. The odontogenic potential must consist of a unique combination of growth factors in different tissue layer at certain stages of tooth development. While currently unknown, it has become a central importance to reveal the basis of the odontogenic potential. Thanks to rapid progress in molecular studies of tooth development, the expression profiles of numerous growth factors at different stages of tooth development have been well documented in mice. While slight differences exist in term of gene expression profiles in the developing tooth between mouse and human [22, 23], the fact that both mouse and human embryonic dental mesenchyme can equally induce tooth formation when recombined with human epithelial cells [19–21, 24] suggests a similar constitution of tooth-inducing signals. It is thus conceivable that an adult cell population that is directed to odontogenic fate with an expression profile of signaling molecules similar to that in an embryonic dental tissue with tooth-inducing capability will act as a “tooth inducer”. Since the dental mesenchyme determines the tooth type and size, it will be preferable to use a mesenchymal cell population as the “tooth inducer”. As outlined in a simplified blueprint of stem cell-based whole tooth regeneration with a scaffold-free approach (Figure 1), it is envisioned that iPSC derived epithelial cells or other appropriate adult cell populations will be prepared as the epithelial component. On the other hand, iPSC derived mesenchymal cells or dental mesenchymal stem cells will be manipulated to acquire odontogenic potential via induction or reprogramming approaches. Recombinants of the epithelial and mesenchymal components will be allowed to develop to the late bud or the early cap stage in vitro prior to being subjected to implantation into an extraction socket in a patient’s jaw. Because of the prolonged human tooth development and differentiation, it may be necessary to accelerate the development of the grafted tooth germ by manipulating gene expression via local application of small inhibitory molecules and growth factors. Ideally, the grafted tooth germs will be able to adjust to the local microenvironment including positional information to develop into a functional tooth. In conclusion, while many problems are waiting to be solved, fast progress in the molecular study of tooth biology and development thanks to new high-throughput technologies will no doubt facilitate realization of implantable bioengineered teeth.Figure 1


Bioengineering of a human whole tooth: progress and challenge.

Zhang Y, Chen Y - Cell Regen (Lond) (2014)

A blueprint of stem cell-based tooth regeneration with a scaffold-free approach. Schematic procedures of stem cell-based scaffold-free tooth regeneration in humans. The procedures include induction of iPSCs or epithelial derived stem cells into epithelial (epi.) sheets and induction of iPSCs or dental mesenchymal (mes.) stem cells into mesenchymal masses with odontogenic potential, tissue recombination, in vitro organ culture of the recombinants to the late bud or early cap stage, implantation of bioengineered tooth germs into the lost tooth sites of patients, and regeneration of functional replacement teeth.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230350&req=5

Fig1: A blueprint of stem cell-based tooth regeneration with a scaffold-free approach. Schematic procedures of stem cell-based scaffold-free tooth regeneration in humans. The procedures include induction of iPSCs or epithelial derived stem cells into epithelial (epi.) sheets and induction of iPSCs or dental mesenchymal (mes.) stem cells into mesenchymal masses with odontogenic potential, tissue recombination, in vitro organ culture of the recombinants to the late bud or early cap stage, implantation of bioengineered tooth germs into the lost tooth sites of patients, and regeneration of functional replacement teeth.
Mentions: Certainly, identification of novel adult human stem cell sources is not yet the final solution for tooth regeneration. Based on the characteristic features of tooth development, to generate an implantable tooth germ in vitro, one of the cell sources, either epithelial or mesenchymal population, must acquire odontogenic potential to initiate regenerative process. In fact, despite the fact that human iPSC-derived epithelial cells [21] as well as human keratinocytes [20] and gingival epithelial cells [19] are able to differentiate into enamel-secreting ameloblasts in response to tooth-inducing signals from the mouse embryonic dental mesenchyme, none of these cell populations possess odontogenic potential. In addition, all the human postnatal mesenchymal stem cells of dental origin identified so far, while capable of differentiating into various types of dental tissues, do not have tooth-inducing capability. Thus conferring cells with odontogenic potential is a major challenge. It is well established that epithelial-mesenchymal interactions are mediated by growth factors, and many growth factors are repeatedly utilized at different stages of tooth development [15]. The odontogenic potential must consist of a unique combination of growth factors in different tissue layer at certain stages of tooth development. While currently unknown, it has become a central importance to reveal the basis of the odontogenic potential. Thanks to rapid progress in molecular studies of tooth development, the expression profiles of numerous growth factors at different stages of tooth development have been well documented in mice. While slight differences exist in term of gene expression profiles in the developing tooth between mouse and human [22, 23], the fact that both mouse and human embryonic dental mesenchyme can equally induce tooth formation when recombined with human epithelial cells [19–21, 24] suggests a similar constitution of tooth-inducing signals. It is thus conceivable that an adult cell population that is directed to odontogenic fate with an expression profile of signaling molecules similar to that in an embryonic dental tissue with tooth-inducing capability will act as a “tooth inducer”. Since the dental mesenchyme determines the tooth type and size, it will be preferable to use a mesenchymal cell population as the “tooth inducer”. As outlined in a simplified blueprint of stem cell-based whole tooth regeneration with a scaffold-free approach (Figure 1), it is envisioned that iPSC derived epithelial cells or other appropriate adult cell populations will be prepared as the epithelial component. On the other hand, iPSC derived mesenchymal cells or dental mesenchymal stem cells will be manipulated to acquire odontogenic potential via induction or reprogramming approaches. Recombinants of the epithelial and mesenchymal components will be allowed to develop to the late bud or the early cap stage in vitro prior to being subjected to implantation into an extraction socket in a patient’s jaw. Because of the prolonged human tooth development and differentiation, it may be necessary to accelerate the development of the grafted tooth germ by manipulating gene expression via local application of small inhibitory molecules and growth factors. Ideally, the grafted tooth germs will be able to adjust to the local microenvironment including positional information to develop into a functional tooth. In conclusion, while many problems are waiting to be solved, fast progress in the molecular study of tooth biology and development thanks to new high-throughput technologies will no doubt facilitate realization of implantable bioengineered teeth.Figure 1

Bottom Line: A major challenge in stem cell-based bioengineering of an implantable human tooth is to identify appropriate sources of postnatal stem cells that are odontogenic competent as the epithelial component due to the lack of enamel epithelial cells in adult teeth.In a recent issue (2013, 2:6) of Cell Regeneration, Cai and colleagues reported that epithelial sheets derived from human induced pluripotent stem cells (iPSCs) can functionally substitute for tooth germ epithelium to regenerate tooth-like structures, providing an appealing stem cell source for future human tooth regeneration.

View Article: PubMed Central - PubMed

Affiliation: Fujian Key Laboratory of Developmental and Neuro Biology, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian Province P.R. China.

ABSTRACT
A major challenge in stem cell-based bioengineering of an implantable human tooth is to identify appropriate sources of postnatal stem cells that are odontogenic competent as the epithelial component due to the lack of enamel epithelial cells in adult teeth. In a recent issue (2013, 2:6) of Cell Regeneration, Cai and colleagues reported that epithelial sheets derived from human induced pluripotent stem cells (iPSCs) can functionally substitute for tooth germ epithelium to regenerate tooth-like structures, providing an appealing stem cell source for future human tooth regeneration.

No MeSH data available.


Related in: MedlinePlus