|Year : 2016 | Volume
| Issue : 2 | Page : 42-52
Stem cells in dentistry, sources, and applications
Mozafar Khazaei1, Azam Bozorgi2, Saber Khazaei3, Abbasali Khademi3
1 Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
3 Torabinejad Dental Research Center, Department of Endodontics, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Web Publication||9-Jun-2016|
Torabinejad Dental Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Introduction: Stem cells (SCs), known as cells with characteristics such as self-renewal and multilineage differentiation, are generally obtained from two sources: Embryonic stem cells (ESCs) and adult stem cells (ASCs). SC research is expected to play a pivotal role in future medicine. The aim of the present review was to introduce dental and nondental SCs, examining the general characteristics, in vivo and in vitro differentiation capacities, immunosuppressive properties as well as the application of SCs in dentistry and regenerative medicine. Methods: In October 2015, PubMed, Scopus were searched by experienced researchers with the query "stem cells and dentistry "and a focus on SC and dental journals. Results: In the field of dentistry, ASCs, isolated from different structures, are divided into different subpopulations: Dental SCs, population of SCs isolated from different components of immature and mature teeth and nondental SCs, and those isolated from oromaxillofacial tissues. Conclusions: It appears that dental and nondental SCs are popular resources of SCs because of easier accessibility and fewer ethical problems. In addition, they have a high differentiation capacity into different cell lineages. Different studies have introduced dental and nondental SCs as suitable SC sources for SC therapy in dentistry and regenerative medicine.
Keywords: Adult stem cells (ASCs), dental stem cells (DSCs), nondental stem cells, regenerative medicine, stem cell (SC)
|How to cite this article:|
Khazaei M, Bozorgi A, Khazaei S, Khademi A. Stem cells in dentistry, sources, and applications. Dent Hypotheses 2016;7:42-52
| Introduction|| |
In the recent decade, the field of stem cell (SC) research has attracted the particular interest of scientists. Recently, various in vivo and in vitro experiments have been conducted to obtain a promising result for the use of SCs in clinical trials. SC biology researchers try to design new therapeutic strategies based on SC therapy, aiming to regenerate tissues and organs injured by diseases. , There are two main types of SCs: Embryonic stem cells (ESCs) and adult stem cells (ASCs). ESCs are multipotent SCs derived from the inner cell mass (ICM) of the embryo. ESC differentiates to form three main germ layers: Ectoderm, mesoderm, and endoderm.  The application of ESCs may be accompanied by ethical problems and may also lead to tumor formation and immune rejection.  ASCs have been characterized in different organs such as the brain, skin, gut, liver, teeth, testis, heart, and various tissues including bone marrow, blood vessels, peripheral blood, skeletal muscle, and ovarian epithelium. 
Dental stem cells (DSCs) are mesenchymal stem cells (MSCs) that are isolated from different components of tooth tissue such as the dental follicle or papilla, with distinct characteristics of self-renewal and a high potential to differentiate into at least three distinct lineages: Adipogenic cells, osteogenic/odontogenic cells, and neurogenic cells. ,,,, DSCs express several markers, including mesenchymal and embryonic SC markers  and neural cell-specific markers, which refer to their neural crest origin.  So far, five various types of DSCs have been isolated from permanent and deciduous teeth in different mature and immature stages of tooth development including dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), stem cells from exfoliated deciduous teeth (SHED), dental follicle progenitor cells (DFPCs), and stem cells from the apical papilla (SCAP) [Figure 1] and [Table 1]. ,,, In this review, the characteristics of these five major types of DSCs will be discussed. Also, we introduce other types of dental stem/progenitor cells and ASCs that could be possibly used in dentistry and regenerative medicine.
| Dental Stem Cells|| |
Dental pulp stem cells
Dental pulp stem cells (DPSCs) with ectomesenchymal origin are the first type of DSCs, isolated from adult dental pulp of the third molar tooth. Although the predominant morphology of DPSC is fibroblast-like because of the presence of different DPSC populations, various morphologies are visible, probably due to the neural crest or mesenchymal origin of DPSCs.  Different subtypes of DPSCs have been identified to express various mesenchymal SC markers. Yang et al.  showed that DPSCs with osteogenic and odontogenic potential express STRO1. Other DPSCs were found to express CD34 and CD117 but not CD45. This population has high osteogenic differentiation potential that makes them capable of differentiating into osteoblasts with a common culture medium supplemented with 20% fetal bovine serum (FBS) and no use of osteogenic-inducing supplements. This population has the ability of in vitro formation of living autologous fibrous bone tissue structure. 
DPSCs express mesenchymal SC markers used to characterize not to isolate DPSCs. These markers include CD29, CD44,  CD73 and CD105,  CD106, CD146, 3G5, and osseo-specific markers such as alkaline phosphatase (ALP), osteopontin, and osteocalcin.  DPSCs express multipotency-related transcription factors Oct4 and Nanog.  Several studies have shown that under certain culture conditions such as addition of beta-glycerophosphate, dexamethasone, and ascorbic acid into the culture medium, DPSCs are able to differentiate into osteoblasts. , Several studies have reported multilineage differentiation capacity of DPSCs into odontoblasts and dentin formation,  neurons, adipocytes, chondrocytes, and muscle cells,  melanoma cells,  hepatocytes, ,, endothelial cells,  in vivo bone or adipose tissue formation  and induced pluripotent stem cells (iPSCs). 
One of the interesting features of DPSCs is their immunosuppressive capacity. DPSCs suppress the proliferation of peripheral blood mononuclear white cells via the production of transforming growth factor beta (TGFB). Treatment with the toll-like receptor 4 (TLR4) agonist reduced the immunomodulatory effects of DPSCs by expressing indolamine-2 and 3-dioxygenase-1 and inhibiting TGFB production.  Kerkis et al.  introduced a subpopulation of DPSCs known as immature DPSCs (IDPSCs). This population expresses ESC-associated markers Nanog, Oct-4, TRA- 1-60, TRA-1-81, SSEA-3, and SSEA-4. It is thought that these cells act as progenitors of DPSCs and SCs from human SHED. The advantage of DPSCs is that their differentiation potential remains even after cryopreservation. ,
Stem cells from human exfoliated deciduous teeth
The growth of permanent teeth is a phenomenon associated with the resorption of the roots of deciduous teeth. The pulp of extracted deciduous teeth serves as an appropriate source of SCs. Multipotent SCs were isolated from the remnant pulp of SHED in 2003.  SHED express different markers in a vast range from ESC markers and antigens such as Nanog, Oct4, SSEA-3, SSEA-4, tumor recognition antigens, including TRA-1-60 and TRA-1-81,  mesenchymal SC surface markers STRO-1 and CD146, neural cell markers beta III tubulin, GAD, NeuN, NFM, nestin, GFAP and CNPase,  stromal- and vascular-associated markers ALP, basic fibroblast growth factor (bFGF), endostatin, matrix extracellular phosphoglycoprotein (MEPE),  and retinal SC marker Pax6. 
An in vitro study on SHED showed that this population has more a proliferative rate and higher adipogenic potential and osteogenic potential than DPSCs.  Higher proliferative rate is assumed to be due to increased levels of telomerase activity.  However, similar to DPSCs, SHED have clonogenic potential as well as differentiation potential into odontoblasts, endothelial cells,  adipocytes, neurons, , hepatocytes,  and iPSC.  Although SHED are unable to form dentin-like structures in vivo,  reviewed by Alok et al.,  they can repair osseous defects of the cranium in animal models, with evidence of bone formation. 
Studies suggest that SHED and neural induced SHED (iSHED) are able to improve spinal cord injury following impaired function in animal models and promote the neural and glial differentiation.  SHED may be used to regenerate the pulp using transplantation of SHED, seeded onto poly-l-lactic acid (PLLA) scaffold, into immunocompromised animal models. Evidence showed that pulp-like tissue and odontoblast-like cells appeared on the surface of the dentin.  Moreover, SHED are reported to inhibit the performance and diminish the number of T helper 17 (Th17) lymphocytes in peripheral blood, and to heighten the ratio of regulatory T lymphocytes (Tregs). 
Werle et al.  isolated SCs from the pulp of carious deciduous teeth (SCCD). They reported that SCCD exhibit a proliferation rate similar to SHED. Also, carious deciduous teeth express typical mesenchymal SC markers CD29, CD73, and CD90. In contrast, SCCD do not express CD14, CD34, CD45, and HLA-DR. SCCD have the potential to differentiate into adipogenic, chondrogenic, and osteogenic lineages.
Stem cells from apical papilla
The apical papilla is a loose connective tissue located at the apex of the root of developing permanent teeth  and differs from the pulp.  In comparison to the dental pulp, the apical papilla contains a richer source of mesenchymal SCs.  During tooth development and crown formation, the dental papilla is converted to dental pulp. In fact, SCAP are isolated at a definite stage of tooth formation. There is a cell-rich zone between the dental papilla and differentiated dental pulp.  There is a strong odontogenic potential in SCAP to form dentin-like structures in vivo. Although DPSCs are a source of odontoblasts producing reparative dentin, it is assumed that SCAP serve as a SC pool of primary odontoblasts contributing to the root dentin formation. 
Although SCAP express different markers, including CD24, CD146, STRO-1, , CD73, CD90, and CD105,  neural cell markers neurofilament M, neuron specific enolase (NSE), NeuN, nestin, bIII tubulin, glutamic acid decarboxylase (GAD), glial fibrillary acidic protein (GFAP) and 2΄, 3΄ cyclic- nucleotide 3΄ phosphodiesterase (CNPase),  increased level of survivin (anti-apoptotic protein),  human telomerase reverse transcriptase (hTERT), lower level of osteogenic/dentinogenic markers dentin sialoprotein (DSP), transforming growth factor beta receptor II (TGF beta RII), matrix extracellular phosphoglycoprotein (MEPE), fibroblast growth factor receptor 3 (FGFR3), fibroblast growth factor receptor 1 (Flg), vascular endothelial growth factor receptor 1 (Flt-1), and melanoma-associated glycoprotein (MUC18), SCAP have a high potential for adipogenic, osteogenic/dentinogenic, and neurogenic differentiation. 
Periodontal ligament stem cells
The periodontal ligament (PDL) is a soft connective tissue, which attaches the teeth to the alveolar bone. PDL plays a significant role in the support and nourishment of teeth and maintains the homeostasis of periodontal tissues and ensures their regeneration.  PDLSCs are multipotent SCs that are isolated by enzymatic digestion or in vitro culture, with the ability to form cementum/PDL-like structures.  It is interesting to know that PDLSCs can be obtained from cryopreserved PDL tissues too. 
PDLSCs express mesenchymal SC markers, including CD146 and STRO-1, similar to DPSCs; however, scleraxis (tendon-specific transcriptional factor) expression occurs at higher levels compared to DPSCs.  Expression of cementoblast/osteoblast-associated markers such as bone sialoprotein, ALP, types I transforming growth factor-b receptor, and osteocalcin have also been reported. Under certain culture conditions, PDLSCs have multipotential capacity to differentiate into various cell lineages including adipocytes, chondrocytes, osteoblasts, ,, neural cells,  and the periodontium. 
PDLSCs were successfully used to improve periodontal defects where they caused the regeneration of the periodontium.  PDLSCs have low immunogenic effects and in response to T-cell energy (T-cell inactivation of function following antigen encounter with low response for a limited time) induced by prostaglandin E2 (PGE2), exhibit immunomodulatory properties.  One study showed that healthy PDLSCs, induced by IFN gamma [released by peripheral blood mononuclear cells (PBMCs)], produce several factors such as indoleamine 2, 3-dioxygenase (IDO), hepatocyte growth factor (HGF), and TGF-b, which, in turn, inhibit the proliferation of PBMCs. In contrast, PDLSCs isolated from the inflamed periodontal ligament were reported to exhibit poor inhibitory effects on the proliferation of T cells. 
An in vitro study indicated that coculture of stimulated PBMCs with inflamed PDLSCs diminishes the potential of PBMCs in preventing Th17 differentiation, inducing Tregs and producing IL-10 and IL-17, indicating the impaired immunomodulatory function of PBMCs in the presence of inflamed PDLSCs.  Silvério et al.  isolated PDLSCs from deciduous teeth (DePDL). This population has more proliferation rate than PDLSCs. In addition, both DePDL and PDSLCs have adipogenic and osteogenic differentiation potential but DePDL seem to exhibit a higher potential for adipogenic differentiation while PDLSCs are typically committed to generate osteogenic lineages.
Dental follicle progenitor/Stem cells
The dental follicle is a condensed ectomesenchymal mass. During the tooth formation and before tooth eruption, dental follicle encloses the developing tooth germ. Dental follicle progenitor/SCs were isolated from the third molar.  Three populations of DFPCs with different morphology are demonstrated as HDF1, HDF2 and HDF3. Among these populations, HDF1and HDF2 cells are morphologically polygonal, whereas HDF2 population shows a spindle-shaped morphology.  Although different populations of DFPCs express mesenchymal SC markers CD29, CD44 and CD105 and do not express hematopoietic markers such as CD34 and CD117, each population has different terms of proliferation rate and mineralization pattern, suggesting that each of them is committed to generate certain lineages.  Also, DFPCs express Notch-1 and Nestin.  DFPCs have a high differentiation potential into chondrocytes, adipocytes and neuron cells, ,, periodontal ligament (PDL), osteoblasts, cementoblasts and fibroblasts. ,
Patil et al.  reported that DFPCs are able to differentiate into functional hepatocyte-like cells (HLCs), obtaining hepatocyte functions such as urea production and glycogen storage. Although in vivo transplantation of DFPCs with ceramic discs showed no evidence of bone, cementum, or dentin formation, generation of cement/immature bone-like structures with the presence of osteocytes/cementocytes was observed.  Immunosuppressive properties of DFPCs were demonstrated where TGFB released by DFPCs quenched the proliferation of PBMCs. Using TLR3 and TLR4 agonists reinforced the immunosuppressive capacity of DFPCs, leading to IL-6 and TGFB secretions. ,
Tooth germ progenitor cells
Tooth germ progenitor cells (TGPCs) are a population of multipotent SCs, which are isolated from the mesenchymal tissue of the third molar tooth germ during the bell stage of tooth development and identified by their high proliferation rate and stable spindle-shaped morphology.  TGPCs express the typical mesenchymal SC markers STRO-1 and CD29, CD44, CD73, CD90, CD105, CD106, CD166 as well as multipotency-related transcription factors such as C- myc, Klf4, Nanog, Oct4, and Sox2. ,, Similar to the other DSCs, TGPCs have adipogenic, chondrogenic, osteogenic/odontogenic, and neurogenic differentiation capacity. ,,, In addition, in vitro studies indicate that TGPCs are able to form tube-like structures, possibly an evidence of vascularization.  Also, TGPCs are able to be induced into hepatocytes, associated with morphology changes from fibroblast-like to epithelial-like ones. Cultured cells express various liver-specific markers such as albumin gene, alpha-fetoprotein (AFP), and cytokeratin19 (CK19). 
| Nondental Stem Cells|| |
Oral mucosa-derived stem cells
The oral mucosa comprises a nonkeratinized stratified squamous epithelium and vascularized lamina propria.  There are two types of ASCs within the mucosa lining the oral cavity. One of them is a population of unipotent small keratinocytes with a size smaller than 40 mm and clonogenic potential,  known as the oral epithelial progenitor/stem cells. The other is a type of characterized oral mucosa SCs existing in the lamina propria of the gingiva, gingiva-derived mesenchymal SCs (GMSCs), which show self-renewal, clonogenic, and multipotent differentiation potential similar to BMSCs but exhibit a faster proliferation rate.  GMSCs represent a stable morphology and retain mesenchymal SC characteristics during continuous passages. 
GMSCs have been reported to have immunomodulatory features.  GMSCs express different mesenchymal SC markers CD29, CD44, CD73, CD90, CD105, CD106, CD146 and CD166. On the other hand, transcription factors Nanog, Nestin, Oct4, Sox2, SSEA-4, and Stro-1 have been shown to be expressed by GMSCs. , In the neural differentiation culture conditions, GMSCs express neural-specific markers including bIII- tubulin, glial fibrillary acidic protein, MAP2, and neurofilament 160/200 (NF-M). 
GMSCs are a neural crest SC-like population with multipotent capacity, which could differentiate into three lineages of germ layers.  GMSCs are also able to differentiate into definitive endoderm (DE) lineage by expressing DE markers such as CRCX4, Fox a2, and Sox17. GMSCs apply their immunomodulatory effect through the secretion of cyclooxygenase 2 (COX-2), IDO, and IL-10.  Furthermore, GMSCs may play an important role in wound-healing using the production of IL-10 and IL-6 and following declined expansion of Th17 cells. 
Salivary gland-derived stem cells
The salivary glands are endoderm-origin structures with exocrine secretion composed of acinar and ductal components lined with epithelial cells. Salivary gland stem/progenitor cells, isolated from humans, , swines,  and rat submandibular glands were found to be highly proliferative and express associated markers of ductal, acinar, and myoepithelial cell lineages.  It has been shown that mouse submandibular gland-derived SCs are able to form floating spheres in vitro, expressing specific SC markers. Transplantation of SCs significantly improved the function of radiation-impaired salivary glands in humans. 
Alveolar bone-derived mesenchymal stem cells
The alveolar bone is an immature, woven bone with embryonically dental follicle origin, keeping the teeth in their site. Matsubara et al.  isolated SCs from the human alveolar bone (hABMSCs). These cells are identified by fibroblast-like morphology and the colonigenic potential of cells. Alveolar bone-derived mesenchymal stem cells (ABMSCs) have been found to express various mesenchymal SC surface markers CD73, CD90, CD105, and STRO-1, whereas they do not express the hematopoietic surface markers CD14, CD34, and CD45. ,, ABMSCs are able to differentiate into osteoblastic lineages, indicated by the high expression of ALP,  chondrocytes, and adipocytes. ,
| Applications of Stem Cells in Dentistry|| |
SC therapy serves as a novel strategy in different medical fields, especially in the field of dentistry and regenerative medicine. Dental and nondental SCs serve as available sources of SCs to be used for clinical applications to improve damages of various diseases such as injuries to the nervous system,  heart infarcts  and muscular dystrophy disorders,  and to regenerate bone tissue. , Recently, SC therapy in dentistry has received more attention.
Regenerating craniofacial defects
Different types of DSCs are used for osseous regeneration. DPSCs are able to generate LAB structure in vitro. Transplantation of LAB tissue leads to lamellar bone forms with the presence of osteocytes in vivo.  Also, implantation of DPSCs, seeded on HA/TCP or poly lactic-co-glycolic acid (PLGA) scaffolds, into animal models generates bone-like tissue. , Moreover, DPSCs loaded on collagen sponge scaffold were used to restore human mandibular bone defects.  Implanted SHED are able to regenerate critical-sized cranial defects with strong evidence of bone formation. 
Honda et al.  demonstrated that transplantation of DFPCs into rats underwent surgically generated, critically-sized bone defects, obviously associated with bone formation. Implantation of SCAP seeded on HA scaffolds into immunodeficient rats showed the formation of mineralized structures similar to bone tissue.  Following the transplantation of scaffold-carried SCAP into immunodeficient mice, a continuous layer of dentin-like deposits was observed.  These results indicate that SCAP can be used for de novo regeneration of dental pulp. In addition to DSCs, some nondental SCs have been proved to regenerate bone impairments. For example, local implantation of GMSCs into animal models may improve calvarial defects and mandibular injuries. 
Regenerating periodontal tissues
DSCs are appropriate candidates for regenerating periodontal tissues. PDLSCs derived from PDL serve as the most suitable sources of SCs used for periodontal therapy. In vitro cultured PDLSCs carried on HA/TCP scaffolds are able to generate a typical periodontal ligament and cementum-like structures.  DFPCs induced by bone morphogenetic protein 2 (BMP-2) were excited to differentiate into odontoblasts and cementoblasts.  The successful regenerative effect of PDL cells have not only been observed in several animal models  but clinical experiments on humans have also presented evidence on the strong potential of application of autologous PDL cells in the treatment of periodontitis  and regeneration of the periodontium. 
Regenerating tooth components
Yang et al.  showed the positive role of DSCs in tooth root regeneration and formation. They reported transplanted DFPCs, seeded on treated dentin matrix (TDM) as biological scaffolds, form root/dentin/pulp-like structures, indicating the successful rate of tooth regeneration. The combination of SCAP and PDLSCs has recently been used to make a normal function of biotooth with an artificial crown. It has been observed that the use of SCAP and PDLSCs is an appropriate choice to provide functional tooth regeneration. 
SCAPs are able to produce odontoblasts, which are responsible for complete root formation in infected immature teeth and promotion of tooth apex formation. SCAP-containing tooth fragments transplanted into animal models led to the appearance of dentin-like deposits onto the wall of dentinal canal.  DPSCs loaded on biodegradable polylactide co-glycolide (PLG) scaffolds were reported to form vascular-rich dentin/pulp-like tissues by administration into the empty root canal.  DPSCs can generate pulp-like tissues with odontoblast-like cells.  It has been indicated xenograft-transplanted SHED, seeded on HA/TCP scaffolds, generate dentin/pulp-like structures with layers of odontoblasts on the mineralized dentin matrix.  SHED seeded onto scaffolds and transplanted into human tooth slices were observed to be able to differentiate into odontoblast-like cells.  Loading SHED onto polylactic acid scaffolds, associated with the presence of transforming growth factor (TGF-b1) and bone morphogenic protein 2 (BMP-2), generated structures similar to pulp tissue components. 
Regenerating nondental tissues
DSCs have been reported to be applied in the regenerative medicine of tissues except for dental tissues. Some of the applications of DSCs in regenerative medicine involve regeneration of muscle and neural tissues, induction of angiogenesis, and treatment of liver diseases.
Regenerating muscle tissue
In vivo studies show that induced SHED is able to form smooth and skeletal muscle cells.  Also, SHED improve the muscular dystrophy in animal models.  DPSCs were reported to repair the infarcted myocardium in rats with acute myocardial infarction. The size of the infarcted region was diminished and vessel formation was increased. It is assumed that DPSCs secrete antiapoptotic and proangiogenic factors. 
Regenerating neural tissue
The role of DSCs in improving the function of injured neural tissue is demonstrated. Administration of DPSCs into the striatum of animal models suffering from middle cerebral artery occlusion (MCAO) significantly improved the neurological dysfunction.  DPSCs differentiated into neurons in vitro and injected into the cortical lesion induced in the brain of rats exhibited properties similar to neurons, indicating the potential of DPSCs in neurogenesis and gliogenesis.  Under neural SC culture conditions, SHED forming neural-like spheres following transplantation into rats suffering from Parkinson's disease somewhat improved the behavioral disorders resulting from apomorphine-evoked rotation.  Both DPSCs and SHED could improve the spinal cord injury of animal models, associated with recovered locomotor functions. ,, Examining the role of tooth germ progenitor cells shows their neuroprotective effects in Alzheimer's and Parkinson's diseases thorough the application of angiogenic, antiapoptotic, and antioxidative mechanisms. 
DPSCs have a high potential to promote angiogenesis/vasculogenesis. Administration of DPSCs into the ischemic mouse model is associated with a high appearance of vessel formation.  Moreover, the three-dimensional (3D) culture of DPSCs with the addition of vascular endothelial growth factor (VEGF) exhibit the formation of endothelial cell-like structures, arranged as capillary-like tubes. 
Treating liver diseases
Examination of carbon tetrachloride (CCl4)-poisoned experimental models with liver injury showed that transplantation of TGPCs into injured animals could inhibit the progression of liver fibrosis and improve liver function. 
Reconstructing corneal epithelium
DSCs are able to form the corneal epithelium following corneal injury. For example, injection of immature DPSCs following total limbal SC deficiency led to corneal epithelium repair.  Reconstruction of the corneal epithelium was also reported via transplantation of SHED, containing tissue-engineered cell sheet, into animal models. 
In spite of various advantages of SCs in dentistry and regenerative medicine, especially DSCs, scientists have recently reported that about 70% of human DSCs cultured in vitro exhibit different karyotypic abnormalities such as polyploidy, aneuploidy, and ring chromosomes as well as high frequency of chromosomal mutations.  These results suggest that cultured DSCs are cytogenically instable and must be carefully analyzed before use in clinical therapy.
| Conclusion|| |
Recently, studies on SC research and therapy have been enforced. This field encompasses different fields of medicine such as dentistry and regenerative medicine. Most of the SCs used in dentistry are obtained from dental structures such as the dental/apical papilla, PDL, and even carious deciduous teeth. Dental SCs have several unique characteristics such as high proliferative rate, vast differentiation potential into different mesenchymal cell lineages, and poor immunogenic effects, making them appropriate sources for SC therapy in regenerative medicine and dentistry. Although DSCs have a lower proliferation rate than ESCs, their clinical application is not associated with in vitro/in vivo tumor formation. Different studies have proven the strong potential of DSCs to generate dental components such as dentin, pulp, cementum and periodontal ligament associated with the presence of functionally active odontoblasts and cementoblasts. DSCs have been reported to form chondrocytes, osteocytes, and adipocytes in vitro. In addition to tooth regeneration, DSCs are capable of regenerating different nondental tissue injuries such as heart diseases, skeletal muscle dystrophy, spinal cord injuries and brain disorders, blood vessels formation, and corneal deficiency recover. Complementary studies are suggested to be conducted to identify the novel aspects of application of DSCs in dentistry and regenerative medicine in particular.
Financial support and sponsorship
This study was financially supported by Kermanshah University of Medical Sciences, Kermanshah, Iran.
Conflicts of interest
Both Mozafar Khazaei and Saber Khazaei have editorial involvement with Dent Hypotheses.
| References|| |
Sylvester KG, Longaker MT. Stem cells: Review and update. Arch Surg 2004;139:93-9.
Bianco P, Robey PG, Simmons PJ. Mesenchymal stem cells: Revisiting history, concepts, and assays. Cell Stem Cell 2008;2:313-9.
Keller GM. In vitro
differentiation of embryonic stem cells. Curr Opin Cell Biol 1995;7:862-9.
Wu DC, Boyd AS, Wood KJ. Embryonic stem cell transplantation: Potential applicability in cell replacement therapy and regenerative medicine. Front Biosci 2007;12:4525-35.
Bissels U, Eckardt D, Bosio A. Characterization and classification of stem cells. Regen Med 2013;1:155-76.
Zhang W, Walboomers XF, Shi S, Fan M, Jansen JA. Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Eng 2006;12:2813-23.
Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al
. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 2004;364:149-55.
Wang X, Sha XJ, Li GH, Yang FS, Ji K, Wen LY, et al
. Comparative characterization of stem cells from human exfoliated deciduous teeth and dental pulp stem cells. Arch Oral Biol 2012;57:1231-40.
Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, et al
. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 2006;1:e79.
Yao S, Pan F, Prpic V, Wise GE. Differentiation of stem cells in the dental follicle. J Dent Res 2008;87:761-71.
Ferro F, Spelat R, D'Aurizio F, Puppato E, Pandolfi M, Beltrami AP, et al
. Dental pulp stem cells differentiation reveals new insights in Oct4a dynamics. PLoS One 2012;7:e41774.
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSC) in vitro
and in vivo
. Proc Natl Acad Sci U S A 2000;97:13625-30.
Morsczeck C, Schmalz G, Reichert TE, Völlner F, Galler K, Driemel O. Somatic stem cells for regenerative dentistry. Clin Oral Invest 2008;12:113-8.
Huang GT, Sonoyama W, Liu Y, Liu H, Wang S, Shi S. The hidden treasure in apical papilla: The potential role in pulp/dentin regeneration and bioroot engineering. J Endod 2008;34:645-51.
Honda MJ, Imaizumi M, Tsuchiya S, Morsczeck C. Dental follicle stem cells and tissue engineering. J Oral Sci 2010;52:541-52.
Yang X, van der Kraan PM, Bian Z, Fan M, Walboomers XF, Jansen JA. Mineralized tissue formation by BMP2-transfected pulp stem cells. J Dent Res 2009;88:1020-5.
Laino G, d'Aquino R, Graziano A, Lanza V, Carinci F, Naro F, et al
. A new population of human adult dental pulp stem cells: A useful source of living autologous fibrous bone tissue (LAB). J Bone Miner Res 2005;20:1394-400.
Jo YY, Lee HJ, Kook SY, Choung HW, Park JY, Chung JH, et al
. Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Eng 2007;13:767-73.
Pivoriuûnas A, Surovas A, Borutinskaite V, Matuzeviccius D, Treigyte G, Savickiene J, et al
. Proteomic analysis of stromal cells derived from the dental pulp of human exfoliated deciduous teeth. Stem Cells Dev 2010;19:1081-93.
Shi S, Bartold PM, Miura M, Seo BM, Robey PG, Gronthos S. The efficacy of mesenchymal stem cells to regenerate and repair dental structures. Orthod Craniofac Res 2005;8:191-9.
Kerkis I, Kerkis A, Dozortsev D, Stukart-Parsons GC, Gomes Massironi SM, Pereira LV, et al
. Isolation and characterization of a population of immature dental pulp stem cells expressing OCT-4 and other embryonic stem cell markers. Cells Tissues Organs 2006;184:105-16.
Liu L, Ling J, Wei X, Wu L, Xiao Y. Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation. J Endod 2009;35:1368-76.
Hsu SH, Chang JC. The static magnetic field accelerates the osteogenic differentiation and mineralization of dental pulp cells. Cytotechnology 2010;62:143-55.
Almushayt A, Narayanan K, Zaki AE, George A. Dentin matrix protein 1 induces cytodifferentiation of dental pulp stem cells into odontoblasts. Gene Ther 2006;13:611- 20.
Stevens A, Zuliani T, Olejnik C, LeRoy H, Obriot H, Kerr-Conte J, et al
. Human dental pulp stem cells differentiate into neural crest-derived melanocytes and have label-retaining and sphere-forming abilities. Stem Cells Dev 2008;17:1175-84.
Ishkitiev N, Yaegaki K, Calenic B, Nakahara T, Ishikawa H, Mitiev V, et al
. Deciduous and permanent dental pulp mesenchymal cells acquire hepatic morphologic and functional features in vitro
. J Endod 2010;36:469-74.
Ishkitiev N, Yaegaki K, Imai T, Tanaka T, Nakahara T, Ishikawa H, et al
. High-purity hepatic lineage differentiated from dental pulp stem cells in serum-free medium. J Endod 2012;38:475-80.
d'Aquino R, Graziano A, Sampaolesi M, Laino G, Pirozzi G, De Rosa A, et al
. Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: A pivotal synergy leading to adult bone tissue formation. Cell Death Differ 2007;14:1162-71.
Zhang W, Walboomers XF, Van Kuppevelt TH, Daamen WF, Van Damme PA, Bian Z, et al
. In vivo
evaluation of human dental pulp stem cells differentiated towards multiple lineages. J Tissue Eng Regen Med 2008;2:117-25.
Yan X, Qin H, Qu C, Tuan RS, Shi S, Huang GT. iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev 2010;19:469-80.
Tomic S, Djokic J, Vasilijic S, Vucevic D, Todorovic V, Supic G, et al
. Immunomodulatory properties of mesenchymal stem cells derived from dental pulp and dental follicle are susceptible to activation by toll-like receptor agonists. Stem Cells Dev 2011;20:695-708.
Papaccio G, Graziano A, d'Aquino R, Graziano MF, Pirozzi G, Menditti D, et al
. Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their differentiated osteoblasts: A cell source for tissue repair. J Cell Physiol 2006;208:319-25.
Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al
. SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA 2003;100:5807-12.
Yamaza T, Kentaro A, Chen C, Liu Y, Shi Y, Gronthos S, et al
. Immunomodulatory properties of stem cells from human exfoliated deciduous teeth. Stem Cell Res Ther 2010;1:5.
Sakai VT, Zhang Z, Dong Z, Neiva KG, Machado MA, Shi S, et al
. SHED differentiate into functional odontoblasts and endothelium. J Dent Res 2010;89:791-6.
Alok A, Singh ID, Singh S, Kishore M. Stem cells: A review. Int J Dent Med Res 2014;1:92-7.
Seo BM, Sonoyama W, Yamaza T, Coppe C, Kikuiri T, Akiyama K, et al
. SHED repair critical-size calvarial defects in mice. Oral Dis 2008;14:428-34.
Taghipour Z, Karbalaie K, Kiani A, Niapour A, Bahramian H, Nasr-Esfahani MH, et al
. Transplantation of undifferentiated and induced human exfoliated deciduous teeth-derived stem cells promote functional recovery of rat spinal cord contusion injury model. Stem Cells Dev 2012;21:1794-802.
Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, et al
. Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 2008;34:962-9.
Werle SB, Lindemann D, Steffens D, Demarco FF, de Araujo FB, Pranke P, et al
. Carious deciduous teeth are a potential source for dental pulp stem cells. Clin Oral Invest 2016;20:75-81.
Sedgley CM, Botero TM. Dental stem cells and their sources. Dent Clin North Am 2012;56:549-61.
Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S, et al
. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: A pilot study. J Endod 2008;34:166-71.
Ding G, Wang W, Liu Y, An Y, Zhang C, Shi S, et al
. Effect of cryopreservation on biological and immunological properties of stem cells from apical papilla. J Cell Physiol 2010;223:415-22.
Bartold PM, McCulloch CA, Narayanan AS, Pitaru S. Tissue engineering: A new paradigm for periodontal regeneration based on molecular and cell biology. Periodontol 2000 2000;24:253-69.
Seo BM, Miura M, Sonoyama W, Coppe C, Stanyon R, Shi S. Recovery of stem cells from cryopreserved periodontal ligament. J Dent Res 2005;84:907-12.
Gay IC, Chen S, MacDougall M. Isolation and characterization of multipotent human periodontal ligament stem cells. Orthod Craniofac Res 2007;10:149-60.
Lindroos B, Mäenpää K, Ylikomi T, Oja H, Suuronen R, Miettinen S. Characterisation of human dental stem cells and buccal mucosa fibroblasts. Biochem Biophys Res Commun 2008;368:329-35.
Xu J, Wang W, Kapila Y, Lotz J, Kapila S. Multiple differentiation capacity of STRO-1+/ CD146+ PDL mesenchymal progenitor cells. Stem Cells Dev 2009;18:487-96.
Li X, Gong P, Liao D. In vitro
neural/glial differentiation potential of periodontal ligament stem cells. Arch Med Sci 2010;6:678-85.
Hasegawa M, Yamato M, Kikuchi A, Okano T, Ishikawa I. Human periodontal ligament cell sheets can regenerate periodontal ligament tissue in an athymic rat model. Tissue Eng 2005;11:469-78.
Ding G, Liu Y, Wang W, Wei F, Liu, D, Fan Z, et al
. Allogeneic periodontal ligament stem cell therapy for periodontitis in swine. Stem Cells 2010;28:1829-38.
Wada N, Menicanin D, Shi S, Bartold PM, Gronthos S. Immunomodulatory properties of human periodontal ligament stem cells. J Cell Physiol 2009;219:667-76.
Liu D, Xu J, Liu O, Fan Z, Liu Y, Wang F, et al
. Mesenchymal stem cells derived from inflamed periodontal ligaments exhibit impaired immunomodulation. J Clin Periodontol 2012;39:1174-82.
Silvério KG, Rodrigues TL, Coletta RD, Benevides L, Da Silva JS, Casati MZ, et al
. Mesenchymal stem cell properties of periodontal ligament cells from deciduous and permanent teeth. J Periodontol 2010;81:1207-15.
Morsczeck C, Götz W, Schierholz J, Zeilhofer F, Kühn U, Möhl C, et al
. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 2005;24:155-65.
Luan X, Ito Y, Dangaria S, Diekwisch TG. Dental follicle progenitor cell heterogeneity in the developing mouse periodontium. Stem Cells Dev 2006;15:595-608.
Machado E, Fernandes MH, Gomes Pde S. Dental stem cells for craniofacial tissue engineering. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:728-33.
Kémoun P, Laurencin-Dalicieux S, Rue J, Farges JC, Gennero I, Conte-Auriol F, et al
. Human dental follicle cells acquire cementoblast features under stimulation by BMP -2/-7 and enamel matrix derivatives (EMD) in vitro
. Cell Tissue Res 2007;329:283-94.
Patil R, Kumar BM, Lee WJ, Jeon RH, Jang SJ, Lee YM, et al
. Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor. Exp Cell Res 2014;320:92-107.
Yagyuu T, Ikeda E, Ohgushi H, Tadokoro M, Hirose M, Maeda M, et al
. Hard tissue-forming potential of stem/progenitor cells in human dental follicle and dental papilla. Arch Oral Biol 2010;55:68-76.
Li Z, Jiang CM, An S, Cheng Q, Huang YF, Wang YT, et al
. Immunomodulatory properties of dental tissue-derived mesenchymal stem cells. Oral Dis 2014;20:25-34.
Morsczeck C, Völlner F, Saugspier M, Brandl C, Reichert TE, Driemel O, et al
. Comparison of human dental follicle cells (DFCs) and stem cells from human exfoliated deciduous teeth (SHED) after neural differentiation in vitro
. Clin Oral Investig 2010;14:433-40.
Ikeda E, Yagi K, Kojima M, Yagyuu T, Ohshima A, Sobajima S, et al
. Multipotent cells from the human third molar: Feasibility of cell-based therapy for liver disease. Differentiation 2008;76:495-505.
Yalvac ME, Ramazanoglu M, Rizvanov AA, Sahin F, Bayrak OF, Salli U, et al
. Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: Implications in neo-vascularization, osteo-, adipo- and neurogenesis. Pharmacogenomics J 2010;10:105-13.
Yalvaç ME, Ramazanoglu M, Tekguc M, Bayrak OF, Shafigullina AK, Salafutdinov II, et al
. Human tooth germ stem cells preserve neuro-protective effects after long-term cryo-preservation. Curr Neurovasc Res 2010;7:49-58.
Yalvaç ME, Yilmaz A, Mercan D, Aydin S, Dogan A, Arslan A, et al
. Differentiation and neuro-protective properties of immortalized human tooth germ stem cells. Neurochem Res 2011;36:2227-35.
Doðan A, Yalvaç ME, ªahin F, Kabanov AV, Palotás A, Rizvanov AA. Differentiation of human stem cells is promoted by amphiphilic pluronic block copolymers. Int J Nanomedicine 2012;7:4849-60.
Garant PR. Oral mucosa. In: Dickson A, editor. Oral Cells and Tissues. Illinois: Quintessence; 2003. p. 81-122.
Egusa H, Sonoyama W, Nishimura M, Atsuta I, Akiyama K. Stem cells in dentistry - Part I: Stem cell sources. J Prosthodont Res 2012;56:151-65.
Zhang Q, Shi S, Liu Y, Uyanne J, Shi Y, Shi S, et al
. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J Immunol 2009;183:7787-98.
Tomar GB, Srivastava RK, Gupta N, Barhanpurkar AP, Pote ST, Jhaveri HM, et al
. Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochem Biophys Res Commun 2010;393:377-83.
Tang L, Li N, Xie H, Jin Y. Characterization of mesenchymal stem cells from human normal and hyperplastic gingiva. J Cell Physiol 2011;226:832-42.
Wang F, Yu M, Yan X, Wen Y, Zeng Q, Yue W, et al
. Gingiva-derived mesenchymal stem cell-mediated therapeutic approach for bone tissue regeneration. Stem Cells Dev 2011;20:2093-102.
Marynka-Kalmani K, Treves S, Yafee M, Rachima H, Gafni Y, Cohen MA, et al
. The lamina propria of adult human oral mucosa harbors a novel stem cell population. Stem Cells 2010;28:984-95.
Zhang QZ, Su WR, Shi SH, Wilder-Smith P, Xiang AP, Wong A, et al
. Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. Stem Cells 2010;28:1856-68.
Lombaert IM, Brunsting JF, Wierenga PK, Faber H, Stokman MA, Kok T, et al
. Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS One 2008;3:e2063.
Sato A, Okumura K, Matsumoto S, Hattori K, Hattori S, Shinohara M, et al
. Isolation, tissue localization, and cellular characterization of progenitors derived from adult human salivary glands. Cloning Stem Cells 2007;9:191-205.
Matsumoto S, Okumura K, Ogata A, Hisatomi Y, Sato A, Hattori K, et al
. Isolation, of tissue progenitor cells from duct-ligated salivary glands of swine. Cloning Stem Cells 2007;9:176-90.
Kishi T, Takao T, Fujita K, Taniguchi H. Clonal proliferation of multipotent stem/progenitor cells in the neonatal and adult salivary glands. Biochem Biophys Res Commun 2006;340:544-52.
Matsubara T, Suardita K, Ishii M, Sugiyama M, Igarashi A, Oda R, et al
. Alveolar bone marrow as a cell source for regenerative medicine: Differences between alveolar and iliac bone marrow stromal cells. J Bone Miner Res 2005;20:399-409.
Mason S, Tarle SA, Osibin W, Kinfu Y, Kaigler D. Standardization and safety of alveolar bone-derived stem cell isolation. J Dent Res 2014;93:55-61.
Park JC, Kim JC, Kim YT, Choi SH, Cho KS, Im GI, et al
. Acquisition of human alveolar bone-derived stromal cells using minimally irrigated implant osteotomy: In vitro
and in vivo
evaluations. J Clin Periodontol 2012;39:495-505.
Pekovits K, Kröpfl JM, Stelzer I, Payer M, Hutter H, Dohr G. Human mesenchymal progenitor cells derived from alveolar bone and human bone marrow stromal cells: A comparative study. Histochem Cell Biol 2013;140:611-21.
Nosrat IV, Widenfalk J, Olson L, Nosrat CA. Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro
, and rescue motoneurons after spinal cord injury. Dev Biol 2001;238:120-32.
Gandia C, Armiñan A, García-Verdugo JM, Lledó E, Ruiz A, Miñana MD, et al
. Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction. Stem Cells 2008;26:638-45.
Kerkis I, Ambrosio CE, Kerkis A, Martins DS, Zucconi E, Fonseca SA, et al
. Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic. J Transl Med 2008;6:35.
Graziano A, d'Aquino R, Cusella-De Angelis MG, De Francesco F, Giordano A, Laino G, et al
. Scaffold's surface geometry significantly affects human stem cell bone tissue engineering. J Cell Physiol 2008;214:166-72.
Graziano A, d'Aquino R, Laino G, Papaccio G. Dental pulp stem cells: A promising tool for bone regeneration. Stem Cell Rev 2008;4:21-6.
Abe S, Yamaguchi S, Watanabe A, Hamada K, Amagasa T. Hard tissue regeneration capacity of apical pulp derived cells (APDCs) from human tooth with immature apex. Biochem Biophys Res Commun 2008;371:90-3.
d'Aquino R, De Rosa A, Lanza V, Tirino V, Laino L, Graziano A, et al
. Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes. Eur Cell Mater 2009;18:75-83.
Huang GT, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS, et al
. Stem/progenitor cell-mediated de novo
regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo
model. Tissue Eng Part A 2010;16:605-15.
Saito N, Takaoka K. New synthetic biodegradable polymers as BMP carriers for bone tissue engineering. Biomaterials 2003;24:2287-93.
Feng F, Akiyama K, Liu Y, Yamaza T, Wang TM, Chen JH, et al
. Utility of PDL progenitors for in vivo
tissue regeneration: A report of 3 cases. Oral Dis 2010;16:20-8.
Nagatomo K, Komaki M, Sekiya I, Sakaguchi Y, Noguchi K, Oda S, et al
. Stem cell properties of human periodontal ligament cells. J Periodontal Res 2006;41:303-10.
Yang B, Chen G, Li J, Zou Q, Xie D, Chen Y, et al
. Tooth root regeneration using dental follicle cell sheets in combination with a dentin matrix-based scaffold. Biomaterials 2012;33:2449-61.
Lee JH, Lee DS, Choung HW, Shon WJ, Seo BM, Lee EH, et al
. Odontogenic differentiation of human dental pulp stem cells induced by preameloblast-derived factors. Biomaterials 2011;32:9696-706.
Gotlieb EL, Murray PE, Namerow KN, Kuttler S, Garcia-Godoy F. An ultrastructural investigation of tissue-engineered pulp constructs implanted within endodontically treated teeth. J Am Dent Assoc 2008;139:457-65.
Yang KL, Chen MF, Liao CH, Pang CY, Lin PY. A simple and efficient method for generating Nurr1-positive neuronal stem cells from human wisdom teeth (tNSC) and the potential of tNSC for stroke therapy. Cytotherapy 2009;11:606-17.
Király M, Kádár K, Horváthy DB, Nardai P, Rácz GZ, Lacza Z, et al
. Integration of neuronally predifferentiated human dental pulp stem cells into rat brain in vivo
. Neurochem Int 2011;59:371-81.
Wang J, Wang X, Sun Z, Wang X, Yang H, Shi S, et al
. Stem cells from human-exfoliated deciduous teeth can differentiate into dopaminergic neuron-like cells. Stem Cells Dev 2010;19:1375-83.
de Almeida FM, Marques SA, Ramalho Bdos S, Rodrigues RF, Cadilhe DV, Furtado D, et al
. Human dental pulp cells: A new source of cell therapy in a mouse model of compressive spinal cord injury. J Neurotrauma 2011;28:1939-49.
Sakai K, Yamamoto A, Matsubara K, Nakamura S, Naruse M, Yamagata M, et al
. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Invest 2012;122:80-90.
Yalvaç ME, Yarat A, Mercan D, Rizvanov AA, Palotás A, ªahin F. Characterization of the secretome of human tooth germ stem cells (h TGSCs) reveals neuro-protection by fine-tuning micro-environment. Brain Behav Immun 2013;32:122-30.
Nakashima M, Iohara K, Sugiyama M. Human dental pulp stem cells with highly angiogenic and neurogenic potential for possible use in pulp regeneration. Cytokine Growth Factor Rev 2009;20:435-40.
Marchionni C, Bonsi L, Alviano F, Lanzoni G, Di Tullio A, Costa R, et al
. Angiogenic potential of human dental pulp stromal (stem) cells. Int J Immunopathol Pharmacol 2009;22:699-706.
Monteiro BG, Serafim RC, Melo GB, Silva MC, Lizier NF, Maranduba CM, et al
. Human immature dental pulp stem cells share key characteristic features with limbal stem cells. Cell Prolif 2009;42:587-94.
Gomes JA, Geraldes Monteiro B, Melo GB, Smith RL, Cavenaghi Pereira da Silva M, Lizier NF, et al
. Corneal reconstruction with tissue-engineered cell sheets composed of human immature dental pulp stem cells. Invest Ophthalmol Vis Sci 2010;51:1408-14.
Duailibi MT, Kulikowski LD, Duailibi SE, Lipay MV, Melaragno MI, Ferreira LM, et al
. Cytogenetic instability of dental pulp stem cell lines. J Mol Histol 2012;43:89-94.
|This article has been cited by|
||Advanced Biomaterials and Techniques for Oral Tissue Engineering and RegenerationA Review
| ||Anamaria Matichescu,Lavinia Cosmina Ardelean,Laura-Cristina Rusu,Dragos Craciun,Emanuel Adrian Bratu,Marius Babucea,Marius Leretter |
| ||Materials. 2020; 13(22): 5303 |
|[Pubmed] | [DOI]|
||Improving pulp revascularization outcomes with buccal fat autotransplantation
| ||Saber Khazaei,Abbasali Khademi,Mahmoud Torabinejad,Mohammad H. Nasr Esfahani,Mozafar Khazaei,Sayed Mohammad Razavi |
| ||Journal of Tissue Engineering and Regenerative Medicine. 2020; |
|[Pubmed] | [DOI]|
||Evaluation of human dental pulp stem cells behavior on a novel nanobiocomposite scaffold prepared for regenerative endodontics
| ||Reza Moonesi Rad,Deniz Atila,Elif Ece Akgün,Zafer Evis,Dilek Keskin,Aysen Tezcaner |
| ||Materials Science and Engineering: C. 2019; 100: 928 |
|[Pubmed] | [DOI]|
||In vitro performance of a nanobiocomposite scaffold containing boron-modified bioactive glass nanoparticles for dentin regeneration
| ||Reza Moonesi Rad,Engin Pazarçeviren,Elif Ece Akgün,Zafer Evis,Dilek Keskin,Sila Sahin,Aysen Tezcaner |
| ||Journal of Biomaterials Applications. 2019; 33(6): 834 |
|[Pubmed] | [DOI]|
||Resveratrol Effect on Adipose-Derived Stem Cells Differentiation to Chondrocyte in Three-Dimensional Culture
| ||Ghazal Keshavarz,Cyrus Jalili,Mona Pazhouhi,Mozafar Khazaei |
| ||Advanced Pharmaceutical Bulletin. 2019; 10(1): 88 |
|[Pubmed] | [DOI]|
||Transforming growth factor-ß1 and runt-related transcription factor 2 as markers of osteogenesis in stem cells from human exfoliated deciduous teeth enriched bone Grafting
| ||Chiquita Prahasanti,Noer Ulfah,IvanIndra Kusuma,Nur Hayati,DiahSavitri Ernawati,Agung Krismariono,Taufan Bramantoro |
| ||Contemporary Clinical Dentistry. 2018; 9(4): 574 |
|[Pubmed] | [DOI]|