Journal of Dental Research and Review

: 2015  |  Volume : 2  |  Issue : 1  |  Page : 47--51

Stem cells: A boon in dentistry

N Deepika1, Sumana Devadiga2, Tanveer Moidin3, Sachin Mittal4, Neha Koshal5,  
1 Department of Oral Medicine and Radiology, K.V.G. Dental College and Hospital, Sullia, Karnataka, India
2 Department of Oral and Maxillofacial Surgery, K.V.G. Dental College and Hospital, Sullia, Karnataka, India
3 Department of Dentistry, Al Hilal Hospital, Muharraq, Kingdom of Bahrain
4 Department of Oral Medicine and Radiology, Shri Bankey Bihari Dental College and Research Centre, Ghaziabad, Uttar Pradesh, India
5 Department of Oral Medicine and Radiology, Swami Devi Dayal Hospital and Dental College, Panchkula, Haryana, India

Correspondence Address:
Dr. N Deepika
Department of Oral Medicine and Radiology, K.V.G. Dental College and Hospital, Sullia, Karnataka


In recent years, there has been a remarkable interest in stem cells within the dental and medical community mainly because of their capability of self-renewal and multiple lineage differentiation. Due to its multipotent properties, stem cells have been employed in the regeneration of body parts and curing various diseases. Stem cells have been isolated from oral and maxillofacial region including tooth, gingiva, periodontium and oral mucosa. Stem cell research and therapy may be used as an alternative to current conventional methods of restoring tooth and craniofacial defects. The objective of this literature review is to provide an overview of the different types of stem cells and their origin and characteristics features and its applications in dentistry. The literature search included PubMed, other indexed journals, and online material.

How to cite this article:
Deepika N, Devadiga S, Moidin T, Mittal S, Koshal N. Stem cells: A boon in dentistry.J Dent Res Rev 2015;2:47-51

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Deepika N, Devadiga S, Moidin T, Mittal S, Koshal N. Stem cells: A boon in dentistry. J Dent Res Rev [serial online] 2015 [cited 2021 Feb 24 ];2:47-51
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Stem cell research has reached new heights in recent times and is implemented in regenerative medicine and dentistry. The human body comprises of cells, which have the ability to undergo renewal or regeneration essential for its existence. Stem cells are capable of developing into different cell types limitlessly, making it helpful in cell-based therapies. This review is undertaken with the objective of providing an overview of stem cells, their characteristics features, and its applications in dentistry. The literature search included PubMed, other indexed journals, and online material.

The term stem cell was proposed by Alexander Maksimov in 1908. [1] They are defined as clonogenic cells which are capable of undergoing self-renewal for long periods and multilineage differentiation, contributing to regenerate specific tissues. [2]

 Properties of Stem Cells

The properties of stem cells are: [3],[4],[5]

Self-renewal - the ability to continuously produce daughter cells with similar characteristicsPotency - ability to differentiateTransdifferentiation or plasticity - ability to exhibit a phenotypic potential that extends beyond the differentiated cell phenotypes of their resident tissueStem cells are also capable of growing in vitro.

 Types of Stem Cells

Stem cells are classified according to their origin and differentiation potential as: [6],[7]

Embryonic stem cells (ESC)Embryonic germ cellsAdult stem cells.

Recently induced pluripotent stem (iPS) cells have been generated artificially via genetic manipulation of somatic cells. These are created by retroviral transcription of genes like Oct4, Nanog, Sox2, Klf4, and c-myc from multipotent stem cells or adult somatic cells. [8],[9] iPS cells can develop into all types of cells from all three germinal layers. [6]

Depending on their regenerative potency, stem cells are further classified as totipotent, pluripotent, or multipotent stem cells. Totipotent cells are capable of generating an entire organism. Pluripotent stem cells are found mostly in embryonic tissues, and also in adult tissues. Multipotent stem cells such as adult stem cells differentiate into cells of different lineages, usually derived from the same germ layer. [8],[10]

 Embryonic Stem Cells

Embryonic stem cells can preserve their ability to differentiate into any cell type while simultaneously maintaining their initial undifferentiated state during cell cycles. This quality of plasticity makes them highly applicable in tissue regeneration. They can differentiate into cells of ectodermal, mesodermal, and endodermal origin. [11] However, the use of ESCs is limited by ethical issues, hence adult stem cells are more favored for their potential applications.

 Adult Stem Cells

Adult stem cells, also called somatic stem cells or postnatal stem cells, can be harvested from different kind of tissues like bone marrow, umbilical cord, amniotic fluid, brain tissue, liver, pancreas, cornea, dental pulp, and adipose tissue. [12] These are quiescent, slow-cycling, undifferentiated cells, surrounded by neighboring cells and extracellular matrix. [13] They make up to 1-3% of the total specialized tissue and include progenitor cells. Progenitor cells are remnants of cell development which can differentiate and proliferate and also replicate. [11] These cells are multipotent in nature and can be isolated easily. However, the mesenchymal stem cells can produce different cell types: Bone, cartilage, fat, muscle, and connective tissues. Immune rejection and teratoma formation is also rare with adult stem cells. [12] Adult stem cells are classified according to their origin as hematopoietic stem cells (HSCs) or mesenchymal cells. [11]

Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) reside in several mesenchymal tissues. HSCs give rise to all the blood cell types whereas MSCs provide stromal support to the HSCs and possess multipotency, as they differentiate to osteoblast, chondrocyte, adipocyte and skeletal myocyte. [6] These cells give rise to intermediate precursor or progenitor cell populations that partially differentiate and commit to various cell lineages. MSCs are the gold standard for identification with typical stem cell markers. The specific marker for the identification isolation factor for MSC is the factor deriving from stromal number 1 (STRO-1). [14] Genetic profiling and immunohistochemical analysis have reported different proportions of perivascular cell markers CD146 (MUC18), CD-44, VCAM-1, and a-smooth muscle-actin-alkaline phosphatase in cells deriving from dental tissue that were positive for STRO-1. [11],[14],[15]

 Stem Cell Niche

Stem niche is a specialized microenvironment housing stem cells, first proposed by Schofield. [16] They have been described as microenvironments that control stem cell function along with stem cell autonomous mechanisms. They maintain a balance between quiescence, self-renewal, differentiation, and the function of definite programs as a reaction to stress. [17] Stem cells are distributed around the body in various niches. Stem niche organizes the self-renewal and differentiation activity of stem cells and is important in tissue maintenance, repair, and regeneration. [17],[18] There are two different stem cell niches in teeth, the cervical loop of rodent incisor for epithelial stem cells and a perivascular niche in adult dental pulp for MSCs though the exact location and molecular regulation is unknown. [13],[15] Soluble molecules such as bone morphogenic proteins (BMPs), wingless-related proteins (Wnt), Notch, fibroblast growth factors (FGF) and Hedgehog proteins are important paracrine regulators of stem cell function which induce proliferation or differentiation. Adult stem cells have limited function without the niche. In bone marrow, the HSCs are located in two different niches (endosteal and perivascular). Notch promotes self-renewal of HSCs. HSCs is regulated by signals derived from stromal fibroblasts and osteoblasts, which form the HSC niche. [19] Metabolic products such as calcium, oxidative stress and levels of reactive oxygen species also affect stem cell function. The ability of the niche to impose functions on stem cells makes them relevant in disease conditions. [20]

 Stem Cell Markers

The common stem cell markers include STRO-1 and STRO-4. STRO-1, a trypsin-resistant cell-surface antigen, is an early surface marker of mesenchymal stem cells. Immature dental pulp stem cells (DPSCs) also express ESC markers such as Nanog, stage-specific embryonic antigen -3 and- 4, Oct-4, antigens such as TRA-1-60 and TRA-1-81. [21],[22] Previous studies have demonstrated that pulp cells express bone markers such as bone sialoprotein, alkaline phosphatase, osteocalcin, and type I collagen. Their differentiation is regulated by various potent regulators of bone formation, including members of the transforming growth factor (TGF-β) superfamily and cytokines. The similarity of the gene expression profiles between DPSCs and precursors of osteoblasts, bone marrow stromal stem cells, has recently been reported. [2]

 Dental Stem Cells

Dental stem cells were first isolated by Gronthos et al. from the dental pulp (DPSCs). [2] Shi and Gronthos isolated stem cells from deciduous teeth and named them stem cells from Human Exfoliated Deciduous teeth (SHED). [15]

Origin: [11],[23],[24],[25]

Periodontal ligament stem cells (PDLSC)Deciduous teethStem cells from the apical papillaAlveolar bone and periosteumDental follicle progenitor stem cellsBuccal mucosa, gingival and muscle.

Numerous growth factors are involved in tooth development. Members of the TGF-β superfamily, BMP-2, and BMP-4 regulate epithelial mesenchymal interactions during odontogenesis. FGF such as FGF-3, FGF-4, FGF-8, and FGF-10 are involved in cell proliferation and regulate expression of specific target genes in teeth. Wnt-3, Wnt-7b, Wnt-10a and Wnt-10b act as regulators of cell proliferation, migration, and differentiation during tooth morphogenesis. Other diffusible factors such as sonic hedgehog contribute to both initiation and dental morphogenesis. During tooth formation, a subpopulation of mesenchymal cells differentiates into odontoblasts, which form primary dentin, promoting tooth morphogenesis. Tooth formation results from epithelial-mesenchymal interactions. Epithelial stem cells give rise to ameloblasts, whereas mesenchymal stem cells form odontoblastic, osteoblastic, cementoblasts, and fibroblasts of the periodontal ligament (PDL). [13],[14] A substantial amount of dental epithelial-mesenchymal stem cells is maintained in the dental pulp and periodontium of both deciduous and permanent teeth. [23] This cell population reduces with age and is consistent with the increase in regenerative capacity observed in younger patients. [11],[15] Recent studies have shown the presence of precursors which are capable of forming odontoblasts in adult dental pulp when stimulated by certain signals such as calcium hydroxide or calcium phosphate materials. [2],[13],[14],[24] Studies have shown that DPSCs exhibit a multipotent character and are derived from neural crest cells and can differentiate into mesenchymal cell lineages in vitro and to some extent, in vivo. [26] This includes osteoblasts, chondrocytes, adipocytes, myocytes, neuronal cells, and cardiomyocytes. [2],[27],[28] The third molars are the universal source of DPSCs. [2] Although the percentage of the dental pulp pluripotent stem cells (pluripotent-like stem cells derived from dental pulp) decreases with age, they are present in older patients. Canines and incisors are a rich source of stem cells in the deciduous dentition. Stem cells can also be obtained from the follicular sac of an unerupted tooth. [1]

 Stem Cells from Human Exfoliated Deciduous Teeth

These cells are comparatively easily accessible, exhibit high plasticity and can be isolated from the pulp of exfoliated deciduous teeth. [24],[29] In vivo SHED cells are capable of inducing bone or dentin formation. These cells are derived from cranial neural crest ectomesenchyme and are identical developmentally and functionally, but they have different gene expression profiles. SHED are immature multipotent stem cells that have higher proliferation rates than DPSCs and bone marrow-derived mesenchymal stem cells. [30],[31] Studies have shown that ex vivo-expanded SHED express STRO-1 and CD146, two early cell-surface markers for bone-marrow-derived MSCs. SHED also express osteoblast/odontoblastic markers, like Runx2, alkaline phosphatase, matrix extracellular phosphoglycoprotein, bone sialoprotein, and dentin sialophosphoprotein. [15],[26]

 Stem Cells from the Dental Follicle

The dental follicle is a loose ectomesenchyme-derived connective tissue sac surrounding the enamel organ and dental papilla of the developing tooth germ before eruption. [32] Dental follicle cells (DFCs) are an attractive source of cells for tissue engineering because they can be easily harvested. They display greater plasticity than other dental stem cells. Morsczeck et al. obtained stem cells from dental follicle of human third molars called dental follicle precursor cells. [33] They express stem cell markers such as Nestin and Notch-1 and can form compact calcified nodules in vitro. [34] Ikeda et al. identified characteristic progenitor cells in the mesenchyme of the third molar tooth germ at the late bell stage with high proliferation activity which were capable of differentiating in vitro into lineages of the three germ layers. [35]

 Stem Cells Derived from Apical Papilla

These dental stem cells, known as stem cells from the root apical papilla (SCAP), are located at the tips of growing tooth roots and are capable of forming odontoblast-like cells in vivo. Recent studies have confirmed that SCAP cells express mesenchymal stem cell markers, including STRO-1, CD146, CD34, CD105, CD24, CD90, and ESC markers, such as Nanog and Oct3/4. SCAP cells are negative for HSC markers, such as CD45 and CD117. [11],[36] SCAP and DPSCs express similar osteo-dentinogenic markers and growth factor receptors. STRO-1 co-expressed with dentinogenic markers such as bone sialophosphoprotein, osteocalcin, growth factors FGFR1 and TGFβRI in cultured SCAP. SCAP also express neurogenic markers such as nestin, neurofilament M, βIII tubulin, NeuN. However, SCAP express fewer amounts of dentine sialoprotein, matrix extracellular phosphorylated protein, TGFβRII, FGFR3. It is likely that SCAP are derived from neural crest cells or at least associated with neural crest cells, similar to DPSCs and SHED. [25] Compared to DPSCs, SCAP cells present much higher and faster proliferation rates, mineralization potential, have more STRO-1 positive cells, higher population doubling levels and an increased capacity for in vivo dental regeneration. [36]

 Periodontal Ligament Stem Cells

The PDL regenerates constantly which involves mesenchymal progenitors. PDLSC and adjacent bone marrow can induce regeneration remotely, and even migrate toward the immature apical region. Recent studies have reported that PDLSCs from the alveolar bone surface displayed superior alveolar bone regeneration compared with PDLSCs from the root surface. [6] PDL consists of growth factors for periodontal regeneration like platelet-derived growth factor (PDGF), epidermal growth factor, FGF, IGF and BMPs. PDGF alone or in combination with the other growth factors encourage periodontal healing and regeneration. It has been shown that BMPs are capable of inducing new alveolar bone and cementum formation. However, BMPs induce the differentiation of cells through an osteogenic pathway, because of which ankylosis are a frequent side-effect. Hence, BMPs have not yet been approved for periodontal applications. [37]

 Bone Marrow-derived Mesenchymal Stem Cells

Embryonic oral epithelium can stimulate an odontogenic response in mesenchyme which does not have a dental origin. [38] Bone marrow-derived mesenchymal stem cells (BMMSCs) are the gold standard MSCs in terms of multipotentiality. However, SCAP and DPSC a different profile of multipotency and are more committed to osteo/dentinogenicity. [25] BMMSCs can be harvested from sternum and iliac crest. It contains hematopoietic and mesenchymal stem cells. The majority of oro-maxillofacial structures are derived from mesenchymal cells. [12] Because these cells have a great potential for bone regeneration, they may be applicable to bone tissue engineering irrespective of the age of the patient. However, several studies have shown a gradual decline in that the osteogenic potential of BMMSCs isolated from the human iliac crest and femur gradual decline with age. [6],[38],[39] D'Ippolito et al.[40] demonstrated that the number and the differentiating potential of bone marrow mesenchymal cells decrease with age, although, Justesen et al. [41] reported that MSC differentiation capacity to osteoblasts and adipocytes was maintained irrespective of donor age. Mandibular bone marrow stem cells possess a high osteogenic potency. The surface markers are similar to the dental pulp including CD44, CD106, and STRO-1. They both express matrix proteins such as alkaline phosphatase, osteocalcin, and osteopontin. However, the growth potential and proliferation rate of DPSCs is superior (30%). This is because the pulp expresses cell cycling mediators such as cyclin-dependant kinase 6 and insulin-like growth factor. [42] Another reason is because DPSC is derived from neural crest cells, whereas BMMSC originates from the mesoderm. [13]

 Oral Mucosa-Derived Stem Cells

The oral mucosa contains two types of adult stem cells. One is the oral epithelial progenitor/stem cells, which are a subpopulation of small oral keratinocytes (smaller than 40 μm). Although they are unipotential, they possess clonogenicity. [6] The other type of stem cells is present in the lamina propria of gingiva, which attaches directly to the periosteum of the underlying bone with no intervening submucosa. Zhang et al. [43] first characterized human gingiva-derived MSCs (GMSCs), which exhibited unique immunomodulatory functions, clonogenicity, self-renewal and multi-potent differentiation capacities similar to that of BMMSCs. GMSCs proliferate faster than BMMSCs, display a stable morphology and do not lose their MSC characteristics. Recent studies have shown that gingival fibroblasts gave rise to iPS cells suggesting that they could be promising for future clinical applications. [37]

 Adipose Tissue Derived Stem Cells

Adipose-derived stem cells (ASC) display multilineage differentiation because of pluripotent mesenchymal stem cells. Adipose tissue is abundant and easily accessible in many individuals. [44] Various animal trials have shown successful periodontal tissue regeneration using ASCs. However, further studies are required in humans for future clinical applications. [45],[46]

 Tissue Engineering

The term "tissue engineering" was coined by Langer and Vacanti in 1993 to describe the process by which tissues and organs are regenerated by cell transplantation with or without a scaffold. The main aim is to design and construct tissues/organs for restoring their function or even replacing them. [37] The aim of regenerative dentistry is to re-create in vitro and ex vivo the processes of embryonic tooth development. Tissue engineering includes three basic mechanisms: Inducting signals, responsive cells, and a matrix/scaffold pulp-like tissue that can be engineered in vitro, using DPSCs seeded into synthetic polyglycolic acid matrices. The scaffolds support the cells and growth factors which enable the progression of biological events in root regeneration. The matrix must allow the stem cells to proliferate and differentiate, and ensure a good neurovascular supply to the new pulp tissue. Biological scaffolds such as collagen and glycosaminoglycan and bone morphogenetic proteins are the major morphogenes for tooth regeneration. [47] Biological scaffolds obtained from natural compounds, such as collagen, offer good biocompatibility and bioactivity; although other synthetic biostructures derived from polylactic acid, polyglycolic acid, sponges, and hydrogels have greater control over degradation processes. [11] Several recombinant growth factors have been introduced for periodontal/bone regenerative therapy, including PDGF and FGF-2, and BMP-2, which can induce bone and cartilage formation. [6] Sonoyama et al. constructed a root/periodontal complex using PDLSCs, SCAP and a hydroxyapatite/tricalcium phosphate scaffold, which was used to support an artificial crown. In addition, cell sheet technology using DFCs in combination with a dentin matrix-based scaffold has been applied successfully to tooth root reconstruction. [48]


Stem cell therapy has a dominant role as a prospective treatment option in dentistry. Dental tissue regeneration provides an alternative to the current conventional restoration therapies. The oral and maxillofacial region is a rich source of adult stem cells. However, several challenges have to be overcome. Though stem cells have generated a large amount of interest, limited clinical trials are available in the field of dentistry. Clearly, there are immunological and ethical problems associated with the use of embryonic cells, thereby limiting its clinical feasibility. Therefore, adult stem cells are preferred. The objective of this review was to provide an overview of the characteristics features of stem cells, and its applications in dentistry. However, more exhaustive research is required, and clinical randomized controlled trials should be conducted before applying such therapeutic modalities which will be beneficial to patients.


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