Role of Adult Stem Cells in

Craniofacial Growth and Repair

Guoqiang Guan,* Songtao Shi,† and Phillip R. Kramer*

Adult stem cells play a role in remodeling and regeneration of tissues and organs through-
out the life of an organism. Data from adult stem cell studies suggested these cells produce
a limited subset of mature cell types; in other words, the cells have limited potency.
However, recent findings suggest that these adult stem cells may be capable of giving rise
to multiple cell types produced from different germ layers. Adult stem cells have been
identified in the craniofacial complex including stem cells from craniofacial bone, dental
pulp, periodontal ligament, and developing tooth bud. Utilization of adult stem cells has
shown these cells to express markers consistent with differentiated tissues and cell types
present within the oral cavity. Currently, studies are using adult stem cells to fabricate new
tissues for replacement and regeneration of lost tissues caused by trauma or disease.
Additional focus is currently on the mechanism by which these stem cells produce differ-
entiated cells expressing protein markers and having function similar to tissues in which
the stem cells were placed. This review discusses discoveries delineating stem cell
potency, the critical roles of adult stem cells in the postnatal growth/development as well
as remodeling, and recent studies utilizing adult stem cells to repair and/or regenerate
craniofacial bone, teeth, periodontium, and temporomandibular joint in clinical protocols.
Semin Orthod 11:227–233 © 2005 Elsevier Inc. All rights reserved.

E mbryonic stem cells are characterized as being pluripo-

tent, that is, they have the potential to develop into many
tissues in the body. As the embryo develops, embryonic stem
cells begin down a path of differentiation and maturity, at
which time they lose this potential.1 Until recently it was
thought that only embryonic stem cells were capable of gen-
erating all the different cell types that contribute to an organ-
ism. However, there is increasing evidence to suggest that
most tissues retain a population of resident stem cells, that is,
adult stem cells, throughout life. Adult stem cells are defined
as the undifferentiated cells that are found in a differentiated
adult tissue,2 residing in a specific area of each tissue where
they remain quiescent in the body until they are activated by
epigenetic and/or environmental factors, such as mechanical
forces, disease, or trauma. Adult stem cell populations serve
*From the Department of Biomedical Sciences, Baylor College of Dentistry,
Texas A&M University System Health Science Center, Dallas, TX.
†Craniofacial and Skeletal Diseases Branch, National Institute of Dental and
Craniofacial Research, National Institutes of Health, Department of
Health and Human Services, Bethesda, MD.
Address correspondence to Phillip R. Kramer, PhD, Texas A&M University
System Health Science Center, Baylor College of Dentistry, Department
of Biomedical Sciences, 3302 Gaston Ave, Dallas, TX 75246; Phone:
214-828-8162; Fax: 214-828-8951; E-mail: pkramer@bcd.tamhsc.edu.
to regenerate multiple tissues that are damaged or are in need
of repair or regeneration.3
Stem cells have been defined in many different ways.
Moreover, the classical definition of a stem cell is changing in
the face of increasing evidence suggesting that stem cells exist
within adult tissues and retain significant phenotypic plastic-
ity (ie, potency). The main principles in the definition of stem
cell include the following: (1) self-renewal, or the ability to
generate at least one daughter cell with characteristics similar
to the initiating cell; (2) multilineage differentiation of a sin-
gle cell; and (3) in vivo functional reconstitution of a given
tissue or cell type.4,5
Tissue repair, which is essential for survival, is a relatively
rapid process involving the usual inflammatory cell cascade,
followed by matrix deposition and then a remodeling process
to heal or regenerate damaged tissues.6 Regeneration involves
slow replacement of tissues via identical cells derived from
progenitor and/or adult stem cells. Previous studies have
identified and isolated adult stem cells from bone, brain,
muscle, and skin that have the potential for differentiation
into various tissues and particularly the cell types present
within the tissues from which the cells were isolated.7-13 Al-
though these cells are quite similar in terms of their differen-
tiation potential, they are different in terms of their growth
properties and perhaps their differentiation lineage prefer-

1073-8746/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. 227
doi:10.1053/j.sodo.2005.07.007
228
ence.14 With these characteristics, scientists have achieved an
alterative approach to investigating the pathogenesis of the
craniofacial deformities and disorders by examination of the
phenotype and possible anomalies in the cultured stem cell.15
More recently, using a repopulation assay in mice Dominici
and colleagues reported that a gene-marked, transplantable
marrow cells from a plastic nonadherent population can gen-
erate both functional osteoblasts/osteocytes and hematopoi-
etic cells.16 These findings indicate that the bone marrow
contains a primitive cell able to generate both the hematopoi-
etic and osteocytic lineages.
Recently, tissue engineering researchers have used adult stem
cells for tissue repair and regeneration. Studies of adult stem
cells demonstrate that multipotent adult progenitor cells
(MAPCs) copurified from bone marrow can differentiate at the
single cell level, not only into mesenchymal cells, but also into
cells/tissues with essential characteristics of embryonic tissues—
visceral mesoderm, neuroectoderm, and endoderm.17 Because
of this, it is now thought that adult stem cells may be more easily
directed toward specific lineages that might be able to give rise to
a wider range of tissues following transplantation than embry-
onic stem cells.11,18
It has been assumed that embryonic stem cells have a
significant advantage over adult stem cells with respect to
tissue regeneration because it was believed that adult stem
cells could differentiate into only a few types of mature tis-
sues, while embryonic stem cells could become a larger vari-
ety of tissues or cell types in the body. However, this notion
has been challenged by increasing empirical findings that
adult stem cells reside in various tissues, including postnatal
bone marrow,11,17 brain,11,19 adipose tissues,20 and mus-
cles9-13 and can differentiate into multiple related tissue
types8,11,21-23 including the periodontium.24 In addition mar-
row-derived stem cells were found to differentiate at the sin-
gle-cell level not only into mesenchymal cell types such as
osteoblasts, chondroblasts, and adipocytes, but also into cells
of visceral mesodermal origin.25 Furthermore, to identify
genes involved in the differentiation pathway that marrow-
derived mesodermal progenitor cells (MPCs) use to form os-
teoblasts, Qi and colleagues examined the expressed gene
profile of undifferentiated MPCs and MPCs induced to form
osteoblasts by cDNA microarray technology.26 As expected,
growth factors, hormones, and signaling pathway genes
known to be involved in osteogenesis were activated during
differentiation. When comparing the gene expression pro-
files of MPCs induced to differentiate into chondroblasts and
osteoblasts, significant differences in the nature and/or tim-
ing of gene activation were seen, indicating that, in vitro, the
mechanism of differentiation of MPCs to one of multiple cell
fates can be determined and that this data can be applied to
defining signals important for lineage-specific differentia-
tion.26 Interestingly, recent studies suggest that the postnatal
craniofacial muscle compartment can be considered an alter-
native to bone marrow and a source of multipotent cells or
muscle-derived stem cells.13
In the past several years, a series of exciting findings high-
lighting the potency and possible clinical application of adult
stem cells have been reported. Potency, in this context, refers
Guan, Shi, and Kramer
to the newly discovered ability of adult stem cells to cross
lineage barriers and to adopt the expression profiles and
functional phenotypes of cells unique to other tissues.27 This
review focuses specifically on craniofacial bone, teeth, peri-
odontium, and the temporomandibular joint (TMJ) within
the craniofacial complex, interpreting the critical roles of
adult stem cells in postnatal growth/development as well as
remodeling and regeneration of the craniofacial tissues or
organs.
Critical Role of Adult Stem
Cells in the Postnatal Growth
and Development of Bone
and the Craniofacial Complex
Adult Stem Cells
and Craniofacial Bone Growth
In general, initial bone formation occurs in two ways—via
intramembranous ossification and endochondral ossifica-
tion. Intramembranous ossification characteristically occurs
embryonically throughout much of the craniofacial skeleton.
However, it also continues in all skeletal structures through-
out life in association with the periosteum. Endochondral
ossification is most characteristic of the postcranial skeleton,
and also occurs within the cranial base and, in a modified
form, in the temporomandibular joint.28 In the postcranial
skeleton and cranial base, cartilage development is initiated
by mesenchymal cell condensation to form primary cartilage
anlaga, followed by chondrocyte maturation processes. As a
final step, cartilage is invaded by blood vessels and osteopro-
genitor cells, and the calcified cartilage is subsequently re-
placed by bone.29 Once the bones structures are formed,
skeletogenesis proceed via the ongoing activities of osteo-
blasts and osteoclasts, which are crucial to its constant re-
modeling and regenerative capabilities.
Sutural development and growth can be perceived as a
specialized form of intramembranous bone growth where
bone cells originate from mesenchymal stem cells located in
the sutural blastema and influenced by the underlying dura
and nasal capsular cartilage.30 Ongoing growth of sutures
depends on the maintenance of a balance between prolifera-
tion of stem cells and their differentiation to form new bone,
so that the stem cell population is maintained until growth of
the skull is complete.30,31 Subtle change of the systemic and
local environment may influence the function of the stem cell
population, and ultimately affects the closure of the suture.
Premature fusion of the sutures leads to skull deformities,
such as scaphocephaly, oxycephaly, and trigoncephaly.32
Similarly, development and growth of the mandibular con-
dyle within the temporomandibular joint, even though it is
characterized by the presence of a cartilage, is best under-
stood as a specialized form of intramembranous skeletal
growth associated with precursor stem cells within its pre-
chondroblastic or proliferative layer.28,33,34 Once formed, all
of bone resorption and deposition are under control of the
periosteum, which depends on the generation of osteoblasts/
Adult stem cells
osteoclasts derived from a progenitor and/or stem cell popu-
lation in its osteogenic layer.
Adult Stem Cells and TMJ Cartilage
The TMJ is enclosed in a capsule that is lubricated with sy-
novial fluid and serves as an important growth site during
postnatal development with two articular surfaces that can
adapt to changing environment conditions.33,35,36 With re-
gard to the glenoid (temporal) fossa, the subarticular osteo-
genic layer of the periosteum provides cartilage and bone
cells for the superior surface of the TMJ.36,37 Mandibular pro-
trusion conducted in a stepwise fashion increased the num-
ber of mesenchymal cells (stem/progenitor cells) in the gle-
noid (temporal) fossa, which in turn shows new cortical bone
formation.38 However, the mandibular condyle is special be-
cause of its ossification of secondary cartilage, and changes its
shape and length by subarticular proliferation of the progen-
itor/stem cells that differentiate into chondrocytes,33,35,39
leading to an earlier formation and increase in the amount of
cartilage matrix, which eventually will be replaced with la-
mellar trabecular bone.36,40 The demonstration of the pres-
ence of chondrogenic stem cells has challenged the concept
that the cartilage growth activity was limited to the first sev-
eral years of life32 and that cartilage has minimal ability to
regenerate, especially in adults.41
Signaling Molecules
Impacting Adult Stem Cells
Adult stem cells have been shown to be modulated by factors
released from cells that function in bone. Heino and col-
leagues used the MLO-Y4 cell line to study the effect of os-
teocytes on the proliferation, differentiation, and bone-form-
ing capacity of bone marrow mesenchymal stem cells.42
There was almost four-fold increase in bone formation and
up to two-fold increase in the proliferation of mesenchymal
stem cells with MLO-Y4 conditioned media, indicating that
conditioned medium from osteocytes stimulates the prolifer-
ation of bone marrow mesenchymal stem cells and their dif-
ferentiation into osteoblasts. Although, there may be several
yet unidentified or unknown factors in osteocyte conditioned
medium, it is conceivable that the signals between osteocytes
and mesenchymal stem cells have an active stimulatory role
in controlling bone formation. It is also reasonable to assume
that there is a renewing source for tissue within the bone
marrow and other tissues and that these cells are activated
and recruited in response to signals from physiological stim-
uli or damaged to tissues throughout the body.3
The proliferation and differentiation of osteoblastic and
osteoclastic progenitor/stem cells are important in the post-
natal growth and development process, being controlled by
local signaling/growth factors and systemic hormones.
Growth factors stimulate cell proliferation and differentiation
by acting through specific receptors on responsive cells. Most
of these growth factors are present and active throughout life,
though they may assume different roles at different develop-
mental or growth periods.43,44 The transforming growth fac-
tor ␤ (TGF␤) pathway occupies a central position in the
229
signaling network that controls the growth, differentiation,
and the final fate of metazoan cells.45 The TGF␤s elicit a wide
variety of biological actions, including embryonic morpho-
genesis, cell proliferation, cell differentiation, and apoptosis,
and are especially important in suture morphogenesis and
growth.46 TGF␤ actualizes its influence on cells by altering
patterns of gene expression such as, c-myc and JunB, which
control cell proliferation.47-49 Furthermore, Warner and col-
leagues demonstrated that TGFá family members are critical
regulators of mammalian orofacial development in that they
are expressed in precise spatiotemporal patterns in the devel-
oping orofacial region and act specifically through control of
cellular proliferation and differentiation in the tissue.49 It is
noteworthy that the growth of craniofacial sutures and fusion
of some skeletal processes depends on maintenance of a bal-
ance between proliferation and differentiation of osteogenic
stem cells to form new bone structures throughout the pro-
cess of skull growth.31
The function of growth hormone on bone is well demon-
strated by the short stature and delayed bone maturation in
children with growth hormone deficiency and in acromegalic
patients with increased cortical bone mass.50,51 Growth hor-
mone is also important for normal adult bone remodeling.
Adults with growth hormone deficiency have reduced bone
mass, and growth hormone treatment increases bone mass in
growth hormone-deficient adults. Studying the effects of
growth hormone on primary cell populations of human peri-
odontal ligament cells and alveolar bone cells, Haase and
colleagues52 reported that the proposed mechanism of
growth hormone action on bone formation is through the
stimulation of osteogenic precursor/stem cell proliferation
and following clonal expansion of these cells, promotion of
differentiation along the osteogenic lineage.
In another study the biological function of dentin matrix
protein 1 (DMP1), an extracellular matrix gene involved in
calcified tooth tissue formation, Narayanan and colleagues
established stable transgenic cell lines and adenovirally in-
fected cells overexpressing DMP1.53 They found that overex-
pression of DMP1 in pluripotent, mesenchyme-derived plu-
ripotent/stem cells can induce these cells to differentiate and
form functional odontoblast-like cells. These studies demon-
strated that functional differentiation of odontoblasts re-
quired a unique set of genes to be turned on and off in a
growth- and differentiation-specific manner.
Adult Stem Cells and
Tooth Eruption and Formation
In the process of tooth eruption, differentiation of osteoblas-
tic and osteoclastic stem cells is absolutely necessary for con-
trolling the synchronous phases of the eruption pathway and
tooth movement. To excavate the eruption pathway by active
alveolar bone resorption the recruitment of osteoclasts is a
prerequisite.54 Proliferation and differentiation of osteoclast
precursor cells may be activated by colony-stimulating factor
1 (CSF-1), nuclear factor kappaB ligand (RANKL), and os-
teoprotegrin (OPG). Activation of transcription factors, cyto-
kines, and growth factors leads to the differentiation of oste-
230
oclasts by the dental follicle in the specialized periosteum
that serves to induce osteogenesis during the formation of
periodontium.54
Shiotani and colleagues investigated RANKL localization
in the periodontal tissues during experimental movement of
rat molars.55 In osteoblasts, osteocytes, and fibroblasts,
RANKL expression was mainly observed in the cytoplasm, in
the cisterna of rough endoplasmic reticulum, and along
plasma membranes. In osteoclasts, RANKL was expressed
along the ruffled, border membranes and in the cytoplasm,
including the clear zone. These findings suggest that during
tooth movement, osteoclast differentiation and activation are
regulated, at least in part, by RANKL, possibly produced by
osteoblasts/stromal cells and osteoclasts themselves in the
periodontal tissues. Thus, tooth eruption and orthodontic
tooth movement requires compression and retraction of the
periodontium to induce proliferation and differentiation of
the stem cell populations causing bone resorption and regen-
eration in this local environment suggesting a potential role
for RANKL in stem cell osteogenic differentiation.
Adult Stem Cells
in the Remodeling,
Repair, and Regeneration
of Craniofacial Structures
The importance of stem cells in craniofacial bone growth and
remodeling has been discussed, but in the following section
the role that stem cells play in repair processes of specific
dental procedures and the future of using engineered tissues
for regeneration of damaged oral structures will be covered.
Topics will include describing the current use of endogenous
stem cells in orthodontic procedures, distraction procedures,
and implants. Then a discussion of current studies using stem
cells to engineer tissues such as fully functioning teeth and a
functioning periodontium will be described.
Endogeneous Adult Stem Cells and
Remodeling and Regenerating Oral Tissues
Bone remodeling of the craniofacial complex and structural
rebuilding during orthodontic and orthopedic treatment is a
complicated process in which bone formation and bone re-
sorption are closely coupled. Alveolar bone within the max-
illa and mandible is one of the most actively remodeled parts
of craniofacial complex during normal aging as well as with
inflammation and orthodontic/orthopedic treatment. The
proliferation and differentiation of osteoblastic and osteoclas-
tic progenitor/stem cells are important in the remodeling
process being controlled by local signaling/growth factors
and systemic hormones.
During orthodontic tooth movement, periodontal tissues
experience extensive remodeling. With loading, the peri-
odontal ligament (PDL) is deformed, inducing a response to
this mechanical stimulus.56 Macroscopically, loading results
in alveolar bone resorption and apposition, occurring at the
compression- and tension-side respectively, achieving the
Guan, Shi, and Kramer
Table 1 Potential of Adult Stem Cells to Differentiate into
Craniofacial Cell Types and Structures
Adult Stem Differentiated Cell
Cell Types or
Sources Structures Laboratories
Bone marrow Tooth structures and Paul T. Sharpe69
bone*
Tooth pulp Dentin-, odontoblast-, Songtao Shi21
pulp- structures
PDL Cementum/PDL Songtao Shi24
structures
Tooth bud Tooth structures Pamela C. Yelick66
Bone marrow Hematopoietic cells Edwin M.
and osteoblasts/ Horwitzf16
osteocytes
PDL represents Periodontal Ligament.
Asterisk (*) represents the experimental prerequisite of recombina-
tion with embryonic oral epithelium.
goal of orthodontic tooth movement.57 Subsequently, this
response can activate PDL stem cells24 and/or mesenchymal
stem cells that regulate both the remodeling of periodontal
ligament itself and/or the adjacent alveolar bone.56
Distraction osteogenesis is becoming a method for gener-
ating new bone in the cases of alveolar bone deformities by
progressively distracting bone healing surfaces and it is es-
sentially the bone remodeling procedure include mobiliza-
tion of the osteoblastic/osteoclastic progenitor/stem cells.36,58
Implant placement is a common dental procedure that
may benefit from stem cells, particularly in patients with
severe atrophy of the mandible in which placement of the
implant into the original bone may be impossible.59 Alveolar
bone deformities, craniofacial anomalies are among the most
frequent congenital birth defects in humans. To restore es-
thetics and function to these patients in the situation of in-
sufficient amount of bone and associated tissues, stem cell-
tissue regeneration is an important procedure of craniofacial
therapeutics.60
Tissue Engineering
and the Future of Dentistry
Teeth are the important organs of the craniofacial complex
and tooth regeneration has been a major goal of tissue engi-
neering in the dental field.61 The incidence of tooth agenesis,
including congenital missing teeth in children, is significant
in the craniofacial complex.62-65 Moreover, tooth loss in the
senior adult population is a social health problem66,67; thus,
tooth replacement strategies are of utmost importance to the
dental field. Efforts to regenerate teeth have been conducted
for decades.68 Recently, to assess the potential of an adult
heterogeneous cell population to form teeth, the Sharpe lab-
oratory established recombinations between the nondental
stem cells, for example, bone-marrow-derived cells, and em-
bryonic oral epithelium (Table 1). This combination formed
a very robust explant when transferred to renal capsules and
developed into teeth with associated bone and soft tissues.69
The data showed that the odontogenic process can be initi-
Adult stem cells
ated in nondental cells of different origins, including purified
stem cell populations and a mixed population of adult cells.69
These results suggest that adult stem cell populations can
form bone and teeth by tissue-engineering techniques and
imply that a pure population of stem cells is not necessary.
This may have important implications for the further devel-
opment of these procedures in humans. However, because
these tooth regeneration studies using adult bone marrow
stem cells still rely on the embryonic oral epithelium. What
signals this embryonic epithelium provides and/or whether
these cells participate directly in the odontogenesis remain
open questions. Therefore, if the embryonic epithelium
could be replaced by an appropriate engineered substitute, it
could be possible to create an integrated tooth from adult
stem cells.
Consistent with these results Yelick’s laboratory focused
on bioengineered teeth from cultured tooth bud cells.66,68
Their most recent study demonstrated the capacity to use
cultured tooth bud cells from single-cell suspensions to bio-
engineer mature tooth structures containing both dentin and
enamel.66 Importantly, they demonstrated that transplanta-
tion of younger rat tooth bud cells into syngeneic, adult rat
hosts could lead to the successful use of allografts for tooth
tissue engineering.
One of the main contributing factors to tooth loss is peri-
odontal disease. Often treatment of periodontal tissues does
not completely restore normal tooth attachments after
trauma and disease resulting in ankylosis, root resorption,
and tooth loss. Adult bone marrow mesenchymal stem cells
or multipotent adult progenitor cells can differentiate into
multiple cellular phenotypes that could assist in restoration
of these types of damages. Multiple studies are under way to
look at the feasibility of mesenchymal stem cells in aiding
tissue repair, although a few studies are focusing on tissues in
the oral cavity and the potential for clinical applications in
treating periodontal disease and/or oral trauma.
Since the factors governing the differentiation potential of
tissue derived from stem cells are not clearly understood,
there is a widespread interest in the isolation, characteriza-
tion, and therapeutic potential of stem cells that reside in
postnatal tissues for the purpose of tissue/organ repair and
regeneration.3 Periodontal ligament cells are primarily de-
rived from mesenchyme and using a combination of immu-
nohistochemistry and in situ hybridization, cocultures of
mesenchymal stem cells and periodontal ligament showed a
significant increase in mesenchymal stem cells’ expression of
osteocalcin and osteopontin and a significant decrease in ex-
pression of bone sialoprotein, characteristics of periodontal
ligament.70 These findings indicated that contact or factors
from the periodontal ligament cells induced mesenchymal
stem cells to obtain periodontal-ligament-like characteristics.
Commonly, repair of periodontal ligament appears to in-
volve progenitor cells present in the periodontal region that
are capable of forming fibroblasts, osteoblasts, and cemento-
blasts.71,72 These cells appear clustered near blood vessels in
the periodontal ligament and have characteristics of early
progenitor cells.73 Moreover, progenitor cells in endosteal
spaces potentially migrate from the bone to periodontal lig-
231
ament to form tissues of the periodontium.74 However, it is
unknown if a single progenitor cell type can give rise to all the
tissues of the periodontium. In light of this previous research,
Shi’s research group isolated PDL stem cells (PDLSCs) from
25 surgically extracted human third molars by single-colony
selection and magnetic activated cell sorting.24 The PDLSCs
expressed mesenchymal stem-cell markers STRO-1 and
CD146/MUC18. Under defined culture conditions, PDLSCs
differentiated into cementoblast-like cells, adipocytes, and
collagen-forming cells. Following isolation and marker char-
acterization, the human PDLSCs were transplanted into im-
munocompromised mice and rats. The PDLSCs showed the
capacity to generate a cementum/PDL-like structure and con-
tribute to periodontal tissue repair. These studies suggest that
human PDL contains a population of multipotent postnatal
stem cells that can be isolated and expanded in vitro, provid-
ing a unique reservoir of stem cells from an accessible tissue
resource.24 Therefore, the PDLSCs used in these studies may
represent a heterogeneous stem cell-enriched population that
contains some early uncommitted progenitor cells. Tissue
regeneration mediated by human PDLSCs might have poten-
tial as a practical cellular-based treatment for periodontal
diseases.
Conclusions
Stem cells derived from one adult tissue may serve as progen-
itor cells for other tissues, thus broadening their therapeutic
potential. However, continued research is necessary regard-
ing the apparent potency of adult stem cells and whether
these tissue-resident stem cells constitute a heterogeneous
population of stem cells, each one committed to its own fate,
undergoing proliferation and differentiation into a mature
phenotype once it has received an inductive stimulus suitable
to its specific genetic repertoire, or whether these different
tissues contain stem cells, each of which are truly pluripo-
tent.75 Discovery of the molecular mechanisms that regulate
stem cell behavior remains a necessary challenge for treat-
ment of the craniofacial deformities and disorders.76 More-
over, the extracellular matrix is a complex, dynamic, and
critical component of all tissues. It functions as a scaffold for
tissue morphogenesis, provides cues for stem cell prolifera-
tion and differentiation, promotes the maintenance of differ-
entiated tissues, and enhances the repair response after in-
jury. Biologically active extracellular matrix components may
have use in tissue repair, regeneration and engineering, and
in programming stem cells for tissue replacement.77 There-
fore, modification of the extracellular matrix including the
cell transplantation carrier is one more area of continuing
research necessary to delineating adult stem cell biology.
Adult stem cells actually have been used therapeutically to
treat leukemia since 1980s using bone marrow stem cell
transplantation.78 In recent years, these marrow stem cells
have attracted considerable attention in efforts for repair/
regeneration of tissues and organs.79 Application of bone
marrow stem cells in animal models for repair or regenera-
tion of craniofacial diseases or disorders is an area of current
research. Overall, increasing evidence shed lights of adult
232
stem cell application on debilitate diseases, such as heart
disease,80 cancer,81 neurodegenerative disease,82 and peri-
odontal disease.24
With increased human life expectancy, clinically we may
face more aging seniors with problems in their alveolar bone
or other tissues/organs. Supporting the idea of repair/regen-
eration of tissue or organs using adult stem cells, D’Ippolito
and colleagues83 successfully isolated stem cells from elderly
patients (ie, 72-years of age), indicating stem cells are present
throughout the age of an individual. It was further supported
by demonstrating that adult stem cells exist in the dental
pulps, allowing for regeneration of oral tissues such as ce-
mentum, PDL, and alveolar bone, from the individual’s own
tooth tissue at any age.21-23
Taken together, it is clear that adult stem cells exert a
critical role in the growth/development, remodeling, and re-
pair/regeneration of the craniofacial complex throughout life.
Although stem cell research and clinical utilization of stem
cells are still in the initial phases existing studies strongly
suggest adult stem cell usefulness in future clinical protocols
aimed at repair and regeneration of craniofacial deformities
and disorders in orthodontics and dentofacial orthopedics.
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