77of tooth tissue-derived stem cells, which can differentiate along various dental-cell
lineages, forming odontoblasts, pulp cells, PDL cells, cementoblasts and osteo-
blasts (Huang et al. 2009 ). These dental stem cells and the associated cytokine net-
works that regulate tooth development have been well identified at the molecular
level (Shi et al. 2005 ; Bartold and Narayanan 2006 ). The stem-cell transplantation
and cytokine approach based on stem-cell biology in dental field will be available
for tooth-tissue repair that can achieve one of the promising concepts in the regen-
erative therapy.
5.3.1 Stem-Cell Therapy
5.3.1.1 Dentin-Pulp Tissue Repair
In the tooth development, dental pulp tissue develops from the dental papillae and
comprises of odontoblasts, fibroblasts, blood vessels and peripheral nerves (Avery
2002 ; Nanci 2012 ). Dental pulp stem cells (DPSCs) and stem cells from human
exfoliated deciduous teeth (SHED) have been identified from the dental pulp in
human permanent third molars and exfoliated deciduous teeth, respectively
(Gronthos et al. 2000 ; Miura et al. 2003 ). DPSCs and SHED represent CD146/
STRO-1 expression as an undifferentiated marker and are thought to be dental stem
cells with high proliferative capacities and multi-differentiation into odontoblasts,
adipocytes and neural cells (Yang et al. 2015 ). These stem cells are available for
stem cell-mediated dentin-pulp complex regeneration. Furthermore, DPSCs and
pulp stem-cell subfractions, including CD31−/CD146− side population (SP) cells
and CD105+ cells, which can generate pulp tissue, are candidate cell source for
dentin repair and dental pulp regeneration (Nakashima et al. 2009 ). During tooth
root development, the dental papilla is located apically to the developing pulp which
is known as the apical papilla that is gelatinous soft tissue with few blood vessels
and cellular components. That tissue contains the stem cells of the apical papilla
(SCAP), which have a high proliferative potential based on their high levels of
telomerase activity and ability to differentiate into odontoblasts or adipocytes
(Sonoyama et al. 2006 , 2008 ). SCAP is also able to generate typical dentin-pulp
complex structures after transplantation in vivo and is thus considered a valuable
stem-cell source for tissue repair and tissue engineering (Fig. 5.2a).
5.3.1.2 Periodontal Tissue Repair
Periodontal tissue, which is composed of cementum, PDL and alveolar bone, devel-
ops from the dental follicle tissue, and that establishes a biological connection
through the insertion of the PDL fibre into the cementum and alveolar bone during
tooth root formation (Saito et al. 2009 ; Shimono et al. 2003 ; Foster et al. 2007 ).
PDL-derived stem cells (PDLSCs), which have been identified in adult human PDL
5 Functional Tooth Regeneration