Dental Stem Cell Biology

The fifi
rst report on the presence of stem cells in dental pulp tissues (DPSCs) was
made by Yamamura in the year 1985 (Yamamura 1985).
However, the major breakthrough in dental history was in 2000 when Gronthos and
his team identififi
ed an isolated odontogenic progenitor population from adult dental pulp, which had
the
ability to regenerate a dentin-pulp-like complex (Gronthos et al. 2002; Karamzadeh
and Eslaminejad 2013).
Nevertheless, subsequent studies further isolated stem celllike populations from
various other dental tissue sources , which include stem cells from human exfoliated
deciduous teeth (SHED) (Miura et al.
2003); periodontal ligament stem cells (PDLSCs) (Seo et al. 2004); alveolar bone
derived mesenchy
mal stem cells (Matsubara et al. 2005); dental follicle precursor cells (Morsczecket al.
2005; Kemounetal. 2007); stem cells from dental apical papilla (SCAP)
(Sonoyama et al. 2006); tooth germ progenitor cells (Ikeda et al. 2008), and stem T.C.
Srijaya et al.

Highlights in the history of dental-related stem cells discoveries and depicting their
niche sources (modififi ed from Liu et al. 2015; Karamzadeh and Eslaminejad 2013)
cell from gingiva (GSCs) (Zhang et al.
2009) (Fig. 15.2). All these stem cell sources are easily accessible through no or
minimally invasive procedure, and can be derived from both young and adult patients

Dental Stem Cells as a Promising Source for Cell

Therapy
Growing interest in the fifi eld of stem cell applications arises from the potential to
control their fate and consequently their functions during tissue repair and/or regen
eration (Mitsiadis and Graf 2009).
For any therapeutic implication surrounding cellbased therapies, selecting a suitable
cell source and knowledge on their microenvironment/niche is a pre-requisite.
Thus, any cells that can provide the systematic framework for new cellular
differentiation and tissue growth might be considered as an ideal cell choice as long as
they are guided by appropriate signals and growth factors from
theirmicroenvironment (Srijaya et al. 2012). Further maneuver for f
acilitating tissue regeneration and growth can be made through formation of
new vasculature and scaffolds made of biomaterials or matrix proteins to model and
create three-dimensional structures (Srijaya et al. 2012).
Herein we describe some potential properties of dental MSCs and their biological
characteristics that may be essential for core elements of cell-based therapeutics.
15.4.1 Easy Accessibility
Originating from the lineage of neural crest (NC), dental stem cells can be consid
ered as one of the most suitable cell sources in terms of easy accessibility. These
cells can be obtained in non-invasive or minimally invasive ways from teeth that are

Stem Cells in Dentistry: Potential Applications and Perspectives in Clinical

Research
extracted in clinical practices and typically discarded as medical waste (Lensch et al.
2006; Jo et al. 2007).
Considering that approximately 20 deciduous teeth are exfoliated in average human
life and in some instances, unerupted third molars are extracted for clinical or
orthodontic purposes, virtually everyone possesses a rich source of stem cells.

Immature Cell Source

Compared to other MSC sources, dental-derived stem cells, particularly dental pulp
stem cells (DPSCs) hold the status of more immature, youthful form of MSCs next
to umbilical cord- and Wharton's Jelly-derived stem cells (Kashyap2015). In general,
immature MSCs exhibit higher proliferation, differentiation, and regenerative
functions than more mature ones. Thus, dental stem cells may offer a unique stem
cell source for diverse clinical applications

Quick Isolation Procedure

The techniques for isolation, culturing, and differentiation of various MSCs have
prominently advanced over the last decade. Growing evidence demonstrates that
though found in various niches, certain tissues contain more stem cells than others
(De Miguel et al. 2012). Among all the stem cells identififi ed so far from different
tissues, dental pulps are considered as a rich source of MSCs (DPSCs) in regard to
the number of potential stem cells extracted from human tissue samples (Huang et al.
2009). Besides the cell number, enzymatic digestion for isolating stem cells
from dental tissues is less time consuming compared to other MSC sources (Guilak
et al. 2004). These factors allow dental stem cells to be less susceptible to potential
enzymatic stress and expand faster than other cell sources. Therefore, although they
are isolated from a tiny amount of dental tissue, potentially suffifi cient number of
cells can be generated in time for many clinical applications.
Multipotency
Apart from having higher proliferative capacity when compared to other well
known MSCs, such as bone marrow-derived stem cells, DPSCs in particular are an
outstanding cell source considering their multi-potent differentiation potential (Liu et
al. 2015). Apart from their differentiation potential into odontogenic cell types
under in vitro culture conditions, DPSCs have been reported to have the ability to
differentiate into adipocytes, neurons, osteoblasts, chondrocytes, myocytes, cardio
myocytes, melanocytes, and hepatocyte-like cells (Jiang et al. 2012; Liu et al. 2015).

Banking of Dental Stem Cells

Tooth banking is recent emerging trend mainly in developed nations around the
world. To get ready stem cells matched for the patient requiring treatment is key to
the success of cell therapy. If tooth banking system is maturing and proven to be
safe and effective, dental professionals would have great opportunities to make their
patients aware of the potential of new therapeutic sources and encourage them to
store their dental stem cells for future clinical usages. Table 15.2shows the list of
stem cell banks established for dental banking to our knowledge. One advantage of
stem cells from teeth is that there is usually another chance of storing a tooth even
if one opportunity is missed, unlike umbilical cord blood stem cells, which is a
once-in-a-lifetime opportunity at each birth. As a child would lose 20 milk teeth
A model of functional therapeutic approaches in dental-derived stem cell-based
therapy under in vivo and in vitro models

over a period of approximately fifi ve years, this length of time assures more opportu
nities for banking the most viable dental stem cells. In addition, teeth extracted for
adults also provide the source of banking. Furthermore, unlike bone marrow and
other tissues-derived stem cell collection, these cells can be harvested with minimal
controversy, in relatively inexpensive and non-invasive manners.
Interestingly, researchers using induced pluripotent (iPS) technology also proved
DPSCs as a perfect cell source for effifi ciently generating high quality iPS cells, mak
ing
it suitable for iPS cell banking. Additionally, in their study data out of 107 DPSC
lines used for determining HLA types, 2 DPSC lines showed homozygous for all 3
HLA loci. This suggests that banking of iPS cell lines generated from these DPSCs
alone can cover approximately 20 % of the Japanese population with a perfect match
(Tamaoki et al.
2010
). Currently our group is undertaking iPS cell generation stud
ies with dental stem cells such as DPSCs. W
e noticed that the reprogramming of
DPSCs into iPSCs is highly effifi cient with both viral and non-viral methods when
compared to other cell sources. To understand the molecular basis of the superior
reprogramming effifi ciency of DPSCs, we are undertaking epigenetic studies and
identifying genetic and epigenetic propensities that render them back to the pluripo
tent state. Thus, our current research in induced pluripotency can further demon
strate the promising potential of DPSC collection as a source of cells for stem cell
banking as well as iPS banking for their future use in regenerative medicine.