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patient’s own cells for regenerative therapy to avoid immunological rejection. In the
dental field, recent studies of stem-cell biology have led to the identification of can-
didate cell sources for tooth-tissue repair and whole-tooth replacement therapy
(Huang et al. 2009 ; Egusa et al. 2012 ). Tooth tissue-derived stem cells, including
DPSCs, SHED, SCAP, PDLSCs and dental follicle stem cells, can differentiate into
several dental-cell lineages and also contribute to the turnover and supply of various
progenitor cells (Huang et al. 2009 ; Egusa et al. 2012 ). These cell linages would be
useful for stem-cell transplantation therapy aimed towards tooth-tissue repair; how-
ever, the tooth-inducible cells, which are able to replicate an epithelial- mesenchymal
interaction in tooth organogenesis, have not yet been identified (Egusa et al. 2012 ,
2013 ). In the future, the tooth-inducible cell sources for whole- tooth regeneration
must be identified from the various tissue-derived stem-cell populations isolated
from patients (Egusa et al. 2013 ). Pluripotent stem cells including ES cells and iPS
cells are also candidate cell sources that can differentiate into endodermal, ectoder-
mal and mesodermal cell linages (Yan et al. 2010 ). Recently, iPS cells have been
established from several oral tissues such as pulp, PDL, gingiva and oral mucosa,
and they have represented the ability to differentiate into dental epithelial or mesen-
chymal cells (Egusa et al. 2010 ; Arakaki et al. 2012 ; Otsu et al. 2012 ). Furthermore,
the identification of critical regulated genes for reprogramming non-dental cells to
differentiate into dental epithelial-mesenchymal stem cells is considered to be an
important direction for future tooth regenerative therapy.
The different tooth types such as incisors, canines, premolars and molars have
distinctive morphological features that are programmed at predetermined sites in
the oral cavity during tooth development. Several studies have proposed molecular
mechanisms for tooth morphology regulation (Cai et al. 2007 ). Not only tooth size/
length but also crown/root shape are important aspects upon generating a bioengi-
neered tooth with proper functional occlusion and aesthetics. Further studies are
required to develop a bioengineering technology that can regulate tooth morphol-
ogy, including tissue engineering using scaffolds and the identification of
morphogenesis- related genes/cytokines to achieve the appropriate morphogenesis.
Tooth regenerative therapy is now regarded as a viable model for studying future
organ replacement regenerative therapies that can be applied to several complex
organs, and it will contribute substantially to the knowledge and technology of
organ regeneration (Volponi et al. 2010 ; Oshima and Tsuji 2014 ).
Acknowledgements This work was partially supported by the Health and Labour Sciences
Research Grants from the Ministry of Health, Labour, and Welfare (no. 21040101) awarded to
Akira Yamaguchi (Tokyo Medical and Dental University), a Grant-in-Aid for Scientific Research
(A) (no. 20249078) awarded to T. Tsuji (2008–2010) and a Grant-in-Aid for Young Scientists (B)
awarded to M. Oshima from the Ministry of Education, Culture, Sports and Technology, Japan.
This work was also partially supported by the Organ Technologies, Inc.
Conflict of Interest M. Oshima and T. Tsuji have no competing interest.
M. Oshima and T. Tsuji