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SYSTEMATIC REVIEW
Year : 2016  |  Volume : 7  |  Issue : 2  |  Page : 42-52

Stem cells in dentistry, sources, and applications


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 Publication9-Jun-2016

Correspondence Address:
Saber Khazaei
Torabinejad Dental Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2155-8213.183764

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  Abstract 

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

How to cite this URL:
Khazaei M, Bozorgi A, Khazaei S, Khademi A. Stem cells in dentistry, sources, and applications. Dent Hypotheses [serial online] 2016 [cited 2019 Jun 20];7:42-52. Available from: http://www.dentalhypotheses.com/text.asp?2016/7/2/42/183764


  Introduction Top


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. [1],[2] 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. [3] The application of ESCs may be accompanied by ethical problems and may also lead to tumor formation and immune rejection. [4] 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. [5]

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. [6],[7],[8],[9],[10] DSCs express several markers, including mesenchymal and embryonic SC markers [11] and neural cell-specific markers, which refer to their neural crest origin. [12] 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]. [7],[13],[14],[15] 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.
Figure 1: Classification of stem cells in dentistry

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Table 1: Dental and non-dental stem cell characterstics


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  Dental Stem Cells Top


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. [12] Different subtypes of DPSCs have been identified to express various mesenchymal SC markers. Yang et al. [16] 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. [17]

DPSCs express mesenchymal SC markers used to characterize not to isolate DPSCs. These markers include CD29, CD44, [18] CD73 and CD105, [19] CD106, CD146, 3G5, and osseo-specific markers such as alkaline phosphatase (ALP), osteopontin, and osteocalcin. [20] DPSCs express multipotency-related transcription factors Oct4 and Nanog. [21] 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. [22],[23] Several studies have reported multilineage differentiation capacity of DPSCs into odontoblasts and dentin formation, [24] neurons, adipocytes, chondrocytes, and muscle cells, [6] melanoma cells, [25] hepatocytes, [11],[26],[27] endothelial cells, [28] in vivo bone or adipose tissue formation [29] and induced pluripotent stem cells (iPSCs). [30]

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. [31] Kerkis et al. [21] 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. [6],[32]

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. [33] 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, [21] mesenchymal SC surface markers STRO-1 and CD146, neural cell markers beta III tubulin, GAD, NeuN, NFM, nestin, GFAP and CNPase, [33] stromal- and vascular-associated markers ALP, basic fibroblast growth factor (bFGF), endostatin, matrix extracellular phosphoglycoprotein (MEPE), [7] and retinal SC marker Pax6. [13]

An in vitro study on SHED showed that this population has more a proliferative rate and higher adipogenic potential and osteogenic potential than DPSCs. [8] Higher proliferative rate is assumed to be due to increased levels of telomerase activity. [34] However, similar to DPSCs, SHED have clonogenic potential as well as differentiation potential into odontoblasts, endothelial cells, [35] adipocytes, neurons, [33],[34] hepatocytes, [26] and iPSC. [30] Although SHED are unable to form dentin-like structures in vivo, [12] reviewed by Alok et al., [36] they can repair osseous defects of the cranium in animal models, with evidence of bone formation. [37]

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. [38] 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. [39] 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). [35]

Werle et al. [40] 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 [41] and differs from the pulp. [42] In comparison to the dental pulp, the apical papilla contains a richer source of mesenchymal SCs. [9] 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. [14] 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. [42]

Although SCAP express different markers, including CD24, CD146, STRO-1, [38],[39] CD73, CD90, and CD105, [43] 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), [38] increased level of survivin (anti-apoptotic protein), [9] 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. [42]

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. [44] PDLSCs are multipotent SCs that are isolated by enzymatic digestion or in vitro culture, with the ability to form cementum/PDL-like structures. [7] It is interesting to know that PDLSCs can be obtained from cryopreserved PDL tissues too. [45]

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. [7] 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, [46],[47],[48] neural cells, [49] and the periodontium. [7]

PDLSCs were successfully used to improve periodontal defects where they caused the regeneration of the periodontium. [50] 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. [51] 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. [52]

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. [53] Silvério et al. [54] 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. [55] 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. [15] 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. [56] Also, DFPCs express Notch-1 and Nestin. [55] DFPCs have a high differentiation potential into chondrocytes, adipocytes and neuron cells, [10],[13],[57] periodontal ligament (PDL), osteoblasts, cementoblasts and fibroblasts. [55],[58]

Patil et al. [59] 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. [60] 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. [61],[62]

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. [63] 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. [63],[64],[65] Similar to the other DSCs, TGPCs have adipogenic, chondrogenic, osteogenic/odontogenic, and neurogenic differentiation capacity. [64],[65],[66],[67] In addition, in vitro studies indicate that TGPCs are able to form tube-like structures, possibly an evidence of vascularization. [64] 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). [63]


  Nondental Stem Cells Top


Oral mucosa-derived stem cells

The oral mucosa comprises a nonkeratinized stratified squamous epithelium and vascularized lamina propria. [68] 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, [69] 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. [70] GMSCs represent a stable morphology and retain mesenchymal SC characteristics during continuous passages. [71]

GMSCs have been reported to have immunomodulatory features. [70] 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. [72],[73] 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). [70]

GMSCs are a neural crest SC-like population with multipotent capacity, which could differentiate into three lineages of germ layers. [74] 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. [70] 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. [75]

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, [76],[77] swines, [78] and rat submandibular glands were found to be highly proliferative and express associated markers of ductal, acinar, and myoepithelial cell lineages. [79] 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. [76]

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. [80] 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. [80],[81],[82] ABMSCs are able to differentiate into osteoblastic lineages, indicated by the high expression of ALP, [80] chondrocytes, and adipocytes. [82],[83]


  Applications of Stem Cells in Dentistry Top


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, [84] heart infarcts [85] and muscular dystrophy disorders, [86] and to regenerate bone tissue. [87],[88] 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. [17] Also, implantation of DPSCs, seeded on HA/TCP or poly lactic-co-glycolic acid (PLGA) scaffolds, into animal models generates bone-like tissue. [87],[89] Moreover, DPSCs loaded on collagen sponge scaffold were used to restore human mandibular bone defects. [90] Implanted SHED are able to regenerate critical-sized cranial defects with strong evidence of bone formation. [37]

Honda et al. [15] 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. [89] Following the transplantation of scaffold-carried SCAP into immunodeficient mice, a continuous layer of dentin-like deposits was observed. [91] 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. [73]

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. [7] DFPCs induced by bone morphogenetic protein 2 (BMP-2) were excited to differentiate into odontoblasts and cementoblasts. [92] The successful regenerative effect of PDL cells have not only been observed in several animal models [51] but clinical experiments on humans have also presented evidence on the strong potential of application of autologous PDL cells in the treatment of periodontitis [93] and regeneration of the periodontium. [94]

Regenerating tooth components

Yang et al. [95] 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. [9]

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. [14] 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. [89] DPSCs can generate pulp-like tissues with odontoblast-like cells. [96] 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. [20] SHED seeded onto scaffolds and transplanted into human tooth slices were observed to be able to differentiate into odontoblast-like cells. [39] 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. [97]

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. [21] Also, SHED improve the muscular dystrophy in animal models. [86] 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. [85]

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. [98] 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. [99] 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. [100] Both DPSCs and SHED could improve the spinal cord injury of animal models, associated with recovered locomotor functions. [38],[101],[102] 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. [103]

Inducing angiogenesis/vasculogenesis

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. [104] 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. [105]

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. [63]

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. [106] Reconstruction of the corneal epithelium was also reported via transplantation of SHED, containing tissue-engineered cell sheet, into animal models. [107]

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. [108] These results suggest that cultured DSCs are cytogenically instable and must be carefully analyzed before use in clinical therapy.


  Conclusion Top


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.

 
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