79tissue, are able to have a highly proliferative capacities and to differentiate into all
of the periodontal cell types after transplantation in vivo (Seo et al. 2004 ). Upon
in vivo transplantation into an immunocompromised animal, PDLSCs were able to
generate cementum and PDL complex structure (Yang et al. 2009 ; Lei et al. 2014 ).
Dental follicle stem cells (DFSCs) were first identified as mesenchymal stem/pro-
genitor cells in the first molars of the neonatal rat, and they have been shown to be
able to differentiate into osteoblasts, cementoblasts, adipocytes and neural cells
(Saito et al. 2005 ; Morsczeck et al. 2005 ; Luan et al. 2006 ; Kémoun et al. 2007 ;
Mehmet et al. 2009 ). These cells are thought to be useful cell types for the regenera-
tion of periodontal tissue injury. In addition, the cell-sheet engineering using stem/
progenitor cells have been developed for clinical use in periodontal tissue regenera-
tion (Guo et al. 2013 ) (Fig. 5.2a).
5.3.2 Cytokine Approach
Deletions of enamel and dentin tissue are most commonly recognised as a tooth
pathological disease due to dental caries or trauma, and the standard treatment
involves the substitution of the natural/physiological dental tissue with artificial
material. Following dental tissue damage, tertiary dentine is deposited with a bio-
logical stimulation in response to dental injury (Smith et al. 1995 ; Bjørndal 2008 ;
Bjørndal and Darvann 1999 ). In particular, reparative dentine formation is a more
complex process requiring initial progenitor/stem-cell recruitment and stimulating
to odontoblast-like cell differentiation and dentine secretion (Sloan and Smith
2007 ; Smith and Lesot 2001 ). Critical molecules, which are likely important in the
regulation of dentin tissue regeneration, have been identified based on epithelial-
mesenchymal interactions in tooth developmental process. It was reported that bio-
active growth factors including transforming growth factor-β (TGF-β) superfamily,
insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), bone
morphogenic proteins (BMPs) and various angiogenic growth factors had a potential
for stimulating odontoblast-like cell differentiation and dentine matrix formation
Fig. 5.2 (continued) * Abbreviations: PDLSCs periodontal ligament stem cells; DFSCs dental
follicle stem cells; PDGF platelet-derived growth factor; IGFs insulin-like growth factors; BDNF
brain-derived neurotrophic factor; bFGF basic fibroblast growth factor; ADAMTSL6β A disinteg-
rin-like metalloprotease domain with thrombospondin type I motifs like 6β; DPSCs dental pulp
stem cells; SHED stem cells from human exfoliated deciduous teeth; SCAP stem cells from apical
papilla; BMPs bone morphogenetic proteins; TGF-β transforming growth factor-β; NGF nerve
growth factor; VEGF vascular endothelial growth factor; GDNF glial cell line-derived neuro-
trophic factor.
(b) Bioengineered root regeneration using a root-shaped hydroxyapatite/tricalcium phosphate
(HA/TCP) carrier, which was loaded with SCAP cells that were covered with gelfoam/PDLSCs,
has been reported to form a root-like structure to which the porcelain crown and core were restored,
resulting in normal tooth function
5 Functional Tooth Regeneration