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REVIEW ARTICLE
Year : 2015  |  Volume : 9  |  Issue : 2  |  Page : 41-50

Application of dental stem cells in regenerative medicine


1 Department of Prosthodontics and Crown and Bridge, Hitkarini Dental College and Hospital, Jabalpur, India
2 Department of Oral Pathology and Microbiology, Hitkarini Dental College and Hospital, Jabalpur, India
3 Department of Oral and Maxillofacial Surgery, Hitkarini Dental College and Hospital, Jabalpur, India
4 Department of Prosthodontics and Crown and Bridge, People's College of Dental Science and Research Centre, Bhopal, Madhya Pradesh, India
5 Department of Endodontics and Operative Dentistry, Bhabha College of Dental Sciences, Bhopal, Madhya Pradesh, India

Date of Web Publication2-Mar-2016

Correspondence Address:
Suryakant C Deogade
Flat No. 502, Block-D, Apsara Apartment, South Civil Lines, Pachpedi Road, Jabalpur - 482 001, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0331-3131.177944

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   Abstract 

Recent discoveries in the field of stem cells place dental professionals at the forefront of helping their patients with potentially life-saving therapies derived from a patient's own stem cells obtained from deciduous or permanent teeth. Stem cells have opened doors of great hope in that these cells produced in large quantities through cell cultures could be injected into failing tissues and organs, which would replace these damaged cells with fresh ones. The emerging field of personalized medicine has focused on the ability of stem cells to grow and regenerate tissues using a patient's own stem cells for biologically compatible therapies and individually tailored treatments. This review discusses the information available on the different types of dental stem cells (DSCs) and their potential role in both dental and medical regenerative therapies.

Keywords: Dental stem cell (DSC), differentiation, regeneration, tissue engineering


How to cite this article:
Deogade SC, Ghate S, Dube G, Nitin SK, Dube P, Katare U, Katare D, Damade S. Application of dental stem cells in regenerative medicine. Ann Nigerian Med 2015;9:41-50

How to cite this URL:
Deogade SC, Ghate S, Dube G, Nitin SK, Dube P, Katare U, Katare D, Damade S. Application of dental stem cells in regenerative medicine. Ann Nigerian Med [serial online] 2015 [cited 2020 Aug 12];9:41-50. Available from: http://www.anmjournal.com/text.asp?2015/9/2/41/177944

were isolated in 2000. [6] Several authors then isolated four more types of MSC-like cells from different dental tissues such as the pulp of exfoliated deciduous teeth, [7] periodontal ligament (PDL), [8] apical papilla, [9] and dental follicle (DF) of wisdom teeth. [10] In this review, the different types of DSCs and their multipotential use in regenerative medicinal perspectives are discussed.


   Dental Pulp Stem Cells Top


Dental pulp stem cells (DPSCs) were the first type of DSCs derived from dental pulp, and were isolated by enzymatic digestion of the pulp tissue of the human-impacted third molars. These multipotential cells exhibited a typical fibroblast-like morphology. [6] The clonogenic nature of these cells was identified that maintained their high proliferation rate even after extensive subculturing. Though no specific biomarker is available for the identification of DPSCs, these cells express several markers including the mesenchymal and bone marrow stem cell markers, STRO-1 and CD146 as well as the embryonic stem cell (ESC) marker, Oct4. The candidate markers of DPSCs include STRO-1, CD29, CD44, CD73, CD90, CD105, CD146, CD166, and CD271. [11]

Some workers cultured DPSCs with various differentiation media and demonstrated their dentinogenic, osteogenic, adipogenic, neurogenic, chondrogenic, and myogenic differentiation potential. [12],[13],[14] Earlier, human DPSCs were transplanted in conjunction with hydroxyapatite/tricalcium phosphate (HA/TCP) powder into immunocompromised mice. [6] After 6 weeks, DPSCs generated a dentin-like tissue lining the surface of the HA/TCP particles that comprised a highly ordered collagenous matrix deposited perpendicular to the odontoblast-like layer. This layer of cells expressed the dentin-specific protein, dentin sialophosphoprotein (DSPP), and extended as tubular structures within newly formed dentin. The collagen matrix resembled the structure of primary dentin with ordered perpendicular fibers rather than reparative dentin, which usually consists of a disorganized matrix. Also, the DPSC transplants contained a fibrous tissue containing blood vessels, similar to the arrangement seen in the dentin-pulp complex in normal human teeth. The stromal-like cells were reisolated from the 3-month-old primary DPSC transplants and transplanted into immunocompromised mice, which generated human alu-immunocompromised positive odontoblasts in mice within a dentin-pulp-like complex containing organized collagen fibers, thus indicating in vivo self-renewal potential of the human DPSCs.

The biological approaches to root canal therapy inspired regenerative endodontics, whereby the infected or necrotic pulp tissues are removed and replaced with regenerated pulp tissue that is capable of revitalizing teeth. [15] Experiments in animal models revealed multilineage differentiation capabilities of DPSCs, which showed their characteristic of maintaining self-renewal and forming pulp-like tissue, odontoblast-like cells, ectopic dentin as well as reparative dentin-like and bone-like tissues. [6],[12] This potential of DPSCs have established their stem cell nature and suggested their promising role in regenerative therapy.


   Stem Cells Derived from Human Exfoliated Deciduous Teeth (SHEDS) Top


The stem cells isolated from the dental pulp of exfoliated deciduous teeth revealed their highly proliferative and clonogenic nature. [7] This was possible with an isolation technique similar to that used in the isolation of DPSCs with two distinct and noticeable differences. The first difference was that these stem cells were isolated from the pulp tissue of the crown of exfoliated deciduous teeth, and the other was that these stem cells did not grow as individual cells and instead exhibited the growth in clusters forming several colonies which, after separation, grew as individual fibroblast-like cells. SHEDs demonstrated their higher proliferation rate and a higher number of colony-forming cells compared to DPSCs. [6],[7] SHEDs expressed early MSC markers (STRO-1 and CD146). [7] The isolation and characterization of SHEDs were studied and it was found that these cells expressed embryogenic stem cell markers such as Oct4, Nanog, stage-specific embryonic antigens (SSEA-3, SSEA-4), and tumor recognition antigens (TRA-1-60 and TRA-1-81). [16],[17] SHEDs demonstrated their multilineage (osteogenic and adipogenic) differentiation potential under different inductive environments. When these cells were cultured with neurogenic inductive media, they developed multiple cytoplasmic processes and expressed different neuronal and glial cell markers such as nestin. [7] This suggested the neural crest origin of these cells. The transplantation of SHEDs into immunocompromised mice showed the formation of dentin-like tissues, which was immune-reactive to dentin-specific sialophosphoprotein antibody. This regenerated dentin was formed due to odontoblast-like cells indicating the odontogenic differentiation potential of SHEDs. SHEDs did not form a dentin-pulp complex after in vivo transplantation, suggesting their different odontogenic differentiation potential from DPSCs. SHEDs, unlike DPSCs, cannot be differentiated into osteoblasts or osteocytes but are able to induce the host cells to undergo osteogenic differentiation. [7] This suggested that SHEDs possess an osteoinductive potential rather than a differentiation capability. Thus, higher proliferation rate and odontogenic and osteogenic differentiation potential make SHEDs well-distinct from the DPSCs and represent their more immature form than DPSCs.


   Periodontal Ligament Stem Cells (PDLSCS) Top


PDL braces the tooth into the alveolar socket and contributes to its nutrition, homoeostasis, and repair. PDL contains different types of cells, which can be differentiated into cementoblasts and osteoblasts. [18],[19] Heterogeneity and continuous remodeling of PDL suggests the presence of progenitor cells, which can form specialized types of cells. The third type of multipotent postnatal stem cells were discovered from the human PDL and were referred to as PDLSCs. [8] PDLSCs were isolated using a similar methodology for DPSCs and SHEDs but the tissues used were from the separated PDL of the roots of impacted human third molar. [8],[20] These isolated cells demonstrated their fibroblast-like morphology and exhibited clonogenic nature. These cells showed a high rate of proliferation compared to that of the DPSCs but were more prolific than the bone marrow MSCs. PDLSCs demonstrated expression of STRO-1, CD146, and a tendon-specific transcription factor (scleraxis). This scleraxis factor was found to be expressed at a higher level in PDLSCs than in DPSCs and bone marrow MSCs. This finding was correlated with the PDL and tendon as both exhibit similar structural compositions of dense collagen fibers and have similar potential to absorb mechanical stress during normal physiological activity. [8]

PDLSCs possessed multilineage differentiation capabilities and were able to undergo osteogenic, adipogenic, and chondrogenic differentiations when cultured with the suitable inductive medium. [8],[20] When PDLSCs were transplanted into immunocompromised mice, a typical cementum-PDL structure was formed. This phenomenon was not observed in the case of DPSCs or bone marrow MSCs. This newly formed PDL-like tissue was composed of type I collagen and interestingly it was connected to the cementum in the same way Sharpey's fibers of the PDL attach to the cementum of the tooth. [8]


   Dental Follicle Precursor Cells (DFPCS) Top


The DF is ectomesenchymal in origin and surrounds the unerupted tooth just like a protective sac. [21] DF controls the osteoclastogenesis and osteogenesis process, which is needed for the eruption of the DF differentiates into the periodontium as the tooth is erupting and becomes visible in the mouth. [21],[22] The periodontium is composed of several types of specialized cells, which suggest the presence of stem cells within the DF that gives rise to the periodontium. The precursor stem cells derived from the DF of the human impacted third molar displayed fibroblast-like morphology expressing various biomarkers (nestin and Notch-1). [10] Several authors conducted in vitro studies and demonstrated the multilineage potential of DFPCs to undergo osteogenic, adipogenic, and neurogenic differentiation. [10],[ 23] When an in vitro neural differentiation of DFPCs and SHEDs was compared, different neural cell marker expression pattern by DFPCs was observed, suggesting their different neuronal differentiation potential. [24] DFPCs showed their potential to differentiate and express cementoblast markers (cementum attachment protein and cementum protein-23) under stimulation by BMP-2 and BMP-7 and enamel matrix derivatives (EMDs). [25]


   Stem Cells of Apical Papilla (SCAPS) Top


While the process of tooth development, the dental papilla develops into the dental pulp and subsequently contributes to the development of the root. The dental papilla progresses apically where it is loosely attached to the developing root. Here it is separated from the differentiated pulp tissue by a cell-rich zone, which contains less blood vessels and cellular components than the pulp tissue and the separating cell-rich zone. [2],[26] A new colony of clonogenic stem cells was isolated that resembled fibroblast-like cells and was further referred to as SCAPs. [9] SCAPs showed a higher proliferation rate than DPSCs. SCAPs express the early mesenchymal surface markers (STRO-1 and CD146). These multilineage cells also express CD24, which could be a unique marker for their population. [9],[26] The potential of SCAPs to differentiate into functional dentinogenic cells was identified. These cells demonstrate their capacity to undergo osteogenic, adipogenic, chondrogenic, and neurogenic differentiation when they are cultured in the suitable inductive media. After transplantation of SCAPs into immunocompromised mice in an appropriate carrier matrix, a typical dentin-pulp like structure was formed due to the presence of odontoblast-like cells. [26]


   Role of Dental Stem Cells in Regenerative Medicine Top


The multilineage and dynamic potential of isolated DSCs unearthed their significance in the field of regenerative medicine and tissue engineering [Table 1].
Table 1: Dental stem cells studied for their applications in regenerative medicine

Click here to view



   Dental Stem Cells and Dental Pulp Regeneration Top


Loss of dental pulp leads to tooth fracture and/or periapical disease, which ultimately results in the loss of tooth. Eradication of dental pulp infection is difficult for the host's immune system due to lack of blood supply to the pulp. Partial pulpectomy has proven to be an ineffective treatment as infecting organisms may be left behind. [27],[28] Dental caries or trauma are the most common factors causing infection of adult pulp, which often necessitates root canal therapy of the affected tooth. This therapy involves removal of the entire pulp and disinfection of the pulp cavity, which is later filled with an artificial material such as gutta-percha. In regenerative endodontics, this diseased pulp is removed and replaced with regenerated pulp tissue, capable of revitalizing the tooth. [15]

Discovery of the different types of DSCs led to their potential applications in the regeneration of dental pulp tissue. Dental pulp tissue engineering was attempted with stem cells isolated from exfoliated deciduous teeth. In this, a tooth slice model was used where SHEDs revealed their ability of differentiating into odontoblast-like cells and also endothelial-like cells. [29] In another in vivo study using the same tooth slice model, the subcutaneous transplantation of DPSCs in mice generated the dental pulp-like tissue on collaged scaffold supplemented with dentin matrix protein (DMP)-1. [30] These experiments advocate the potential of SHEDs and DPSCs as reliable and genuine sources of stem cells for the regeneration and tissue engineering of dental pulp tissue.


   Dental Stem Cells and Tooth Regeneration Top


The stem cell-based biological tooth repair and regeneration must consider the generation of the root and its surrounding PDL with its nerve and blood innervations. [31] The replacement of the crown with artificial functioning options makes its reconstruction less important over its root part. Tooth development in mammals passes through a series of interactions between embryonic oral epithelial cells and neural crest-derived mesenchyme. [32],[33] This oral epithelium provides the initial inductive signals to the mesenchyme before the initiation of tooth development. In tooth reconstruction, cell populations from epithelial or mesenchymal origin must have the potential to induce signals to each other. Several researchers [34],[35],[36] conducted in vitro studies on the development of embryonic tooth primordial from adult stem cells combined with embryogenic oral epithelium, adult human gingival epithelial cells combined with embryonic mesenchyme, or harvested cells from tooth buds combined with materials. Transplantation of embryonic tooth primordia in the adult oral cavity can develop into complete teeth and will form roots after an adequate time and erupt into the mouth. [34] Adult DPSCs are derived from the neural crest and these cell populations can be a potential replacement for embryonic mesenchyme in the generation of tooth primordial. Hung et al. [36] (2011) compared the sources of MSCs from the adipose tissue and dental pulp and investigated the DPSCs for tooth regeneration in the alveolar sockets of the rabbit. They noticed no visible tooth eruption in any of the graft sites of the alveolar sockets. Similar comparisons were investigated between bone marrow stromal stem cells and DPSCs. [38] This comparison demonstrated that DPSCs pellet reassociated with adult rat apical bud cells and formed crown-like structures in vivo. These structures showed the distinct regions of the enamel, dentin, predentin, and both ameloblast and odontoblast layers. [38] Yan et al. [38] (2010) could not notice the formation of root-like structures after the transplantation of DPSCs and suggested the future scope of induced pluripotent stem (iPS) cells from DPSCs isolated from a patient's own dental pulp. They reprogrammed human DPSCs into iPS cells using Lin28, Nanog, Oct4, and Sox2 or c-Myc, Klf4, Oct4, and Sox2 and observed that iPS human DPSCs exhibited human ESC (hESC) morphology, expressed hESC markers, and formed embryoid bodies in vitro and teratomas in vivo, containing tissues of all three germ layers. [39]

The MSC-mediated functional tooth (root/periodontal tissue) regeneration was experimented on among swine. [9] The swine SCAPs were seeded onto root-shaped HA/TCP block, which was then coated with gelfoam-containing swine PDLSCs and was inserted in the central incisor socket of swine. After 3 months of transplantation, histological and computerized tomography scan showed a HA/SCAP-gelfoam/PDLSC structure growing inside the socket with mineralized root-like tissue formation and PDL space. These results displayed the potential of combined autologous SCAP/PDLSCs generating a bioroot that indicated an alternative approach to dental implants for replacing missing teeth. More recently, Lee et al. [39] (2014) demonstrated the role of three-dimensional (3D) printed multiphase scaffolds for regeneration of the periodontium complex. DPSCs could produce putative dentin/cementum, PDL, and alveolar bone complex 3D layer-by-layer fabrication of a multiphase scaffold. This could precisely control microarchitecture in different regions in conjunction with spatiotemporal delivery of three recombinant human proteins.


   Dental Stem Cells and Bone Tissue Regeneration Top


DSCs are an alternative approach to bone tissue engineering. A new population of human DPSCs was identified as a useful source of living autologous fibrous bone tissue. [41] These cells were referred to as stromal bone-producing DPSCs (SBP-DPSCs) that differentiated into CD44+/Runx2+ osteoblast precursors and subsequently into osteoblasts with the addition of 20% fetal bovine serum (FBS). Some researchers [42],[43] demonstrated the osteogenic differentiation potential of DPSCs in in vitro and in vivo experiments where they observed the formation of strong alkaline phosphatase and expression of bone-specific markers within the newly formed bone tissue. This osteogenic potential of DPSCs has proposed their use in combination 3D polymeric scaffolds to produce bone-like hard tissues. The formation of a well-mineralized hard tissue with distinct concentric lamellae and a partially developed bone marrow-like hematopoietic tissue was observed during subcutaneous implantation of rat STRO-1-selected DPSCs with 3D porous HA/TCP carrier. [44] It was noted that the addition and transfection of BMP-2 led to the enhancement in the production of mineralized hard tissue. [44] Ikeda et al. [44] (2010) also identified the similar effects, where in vitro cultured DPSCs with recombinant human BMP-2 (rhBMP-2) led to prominent osteoinducibility of DPSCs. This cell population then produced abundant bone-like tissues in vivo. Akkouch et al. [45] (2014) experimented predifferentiated DPSCs onto collagen-hyroxyapatite-poly (L-lactide-co-å-caprolactone) (Col1-HA-PLCL) composite scaffolds, which promoted adhesion, proliferation, and differentiation of the osteoblast-like cells with extracellular matrix mineralization throughout the scaffold. Kanafi et al. [46] (2013) immobilized the DPSCs within alginate microspheres and tested in vitro, the osteogenic differentiation potential of these cells. This immobilization resulted in an enhanced mineralization, protein secretion, and an upregulated osteogenic gene profile. Immobilization also triggered osteogenic differentiation of DPSCs without the use of induction factors in the medium. These in vivo and in vitro studies revealed the potential of DPSCs to form woven bone and well-vascularized lamellar bone. Also, autologous DPSCs seeded onto collagen sponge scaffolds could be used to repair alveolar bone defects. [48] Yamada et al. [49] (2011) implanted DPSCs with platelet-rich plasma (PRP) into bone defects in the mandible and observed a well-formed mature bone, positive for osteocalcin and containing neovascularization. These studies indicated the potential of DPSCs for bone regeneration in oral maxillofacial surgery and craniofacial anomalies. More recently, Annibali et al. [50] (2014) studied the potential use of DPSCs in the regeneration of critical-sized bone defects in a rat calvarial critical defect model in conjunction with a granular deproteinized bovine bone (GDPB) or β-TCP scaffold. They observed an enhanced increase in the bone mineral density when DPSCs were implanted with GDPB scaffold. Similar observations were noted by Maraldi et al. [51] (2013) who used human DPSC-seeded collagen sponges in a rat calvarial critical-sized defect model. They observed the complete bridging of the defect by 8 weeks. The topographical design of biomaterials is crucial for the regulation of DPSC differentiation so that it is used in cell therapies and regenerative medicine. Recently, Kolind et al. [52] (2014) investigated the interaction of pillar-topographical parameters upon attachment, morphology, proliferation, and osteogenic differentiation of DPSCs and observed an enhanced mineralization.


   Dental Stem Cells and Neural Regeneration Top


Ruffins et al. [53] (1998) revealed the formation of ventral neural tube derivatives after transplantation of early cranial neural crest cells (CNCs). Chai et al. [54] (2000) showed the contribution of migrating CNCs in the formation of dental papilla, dental pulp, PDL, and other tissues in the tooth and mandible. It is evident that the different types of DSCs belong to CNC origin. Certain authors supported this fact and revealed that different DSCs expressed neural and neural crest markers with or without induction. [7],[9],[12]

Limitations such as the low incidence of adult neural stem cells (NSCs) and its harvesting diverted the use of bone marrow-derived MSCs (BMMSCs) to stimulate neuroregeneration. However, the efficiency of differentiation and accessibility may limit its application in neurodegenerative disorders. [55] DPSCs can be an alternative approach for neural regeneration as these cells showed expression of ESC pluripotency markers (Oct-4, Nanog, SSEA-4, and TRA-1-60). [56] Kim et al. [57] (2012) observed the potential of DPSCs to express multipotency markers indicating chondrogenic and osteogenic tissue formation and spontaneous neural differentiation. The molecular regulation of DPSC differentiation has been explained as the role of the distal c-terminus of voltage-gated L-type Ca2+ channel in orientating DPSCs differentiation toward the neuronal phenotype. [58] Adult stem cell populations derived from the neural crest would possess a predisposition for neuronal differentiation and repair. [59] Under appropriate environmental cues, DPSCs showed their potential to produce a sodium current consistent with functional neuronal cells. In animal studies, it has been observed that human DPSCs promoted the proliferation and differentiation of endogenous neural stem cells and generated neurospheres in appropriate environmental cues. [60],[61] The transplanted human DPSCs altered the patterns of axonal migration in a receptive host nervous system and also assist in the homing of endogenous neural stem cells to the site of transplantation. [62] Further, the migration of avian trigeminal ganglion axons was observed toward the implanted DPSCs. This phenomenon was due to CXCL12 expression by the DPSCs, which assisted in the homing of endogenous neural stem cells to the site of DPSC transplantation. This experiment suggested a possible evidential role of DPSCs in inducing neuroplasticity within a receptive host nervous system. Nosrat et al. [63] (2001) experimented with dental pulp cells (DPCs) rather than DPSCs and found that the grafting of DPCs promoted survival of injured motor neurons in a rat model of spinal cord injury. Apel et al. [64] (2009) reported a neuroprotective effect of DPCs in models of Alzheimer's and Parkinson's disease. Martens et al. [65] (2013) updated the potential role of DSCs in neural regeneration. The authors stressed the capability of stem cells to produce and secrete growth/neurotrophic factors for the differentiation of endogenous cell types to improve neural tissue regeneration. De Almeida et al. [66] (2011) observed in their study that transplantation of human DPCs into the center of a spinal cord lesion in mice produced larger areas of white matter preservation and better tissue organization. They postulated that the secretion of neurotrophic factors could have led to the stimulation of collateral sprouting improving functional outcomes. Sakai et al. [67] (2012) also reported positive findings where they found improved locomotor recovery after complete transaction of the rat spinal cord followed by human DPSC transplantation at the site of injury. Yamamoto et al. [68] (2014) discussed the multifaceted neuroregenerative potential of human DPSCs and SHEDs in spinal cord injury models. They observed that the microenvironment of transplanted stem cells affects their potential for differentiation. Furthermore, injured spinal cord contains high levels of proinflammatory mediators, which may activate the oligodendrocyte-specific differentiation cascade. DPCs have been suggested as an alternative therapy for peripheral nerve injury.


   Dental Stem Cells and Angiogenesis and Vasculogenesis Top


Isner et al. [69] (1999) suggested the implementation of stem cells and endothelial progenitor cells (EPCs) to stimulate vasculogenesis as an alternative therapy in patients suffering from ischemic disease. Several other authors [70],[71] also revealed the therapeutic benefits of injection of bone marrow-derived or adipose-derived MSCs after myocardial infarction (MI) and other heart diseases.

Gandia et al. [72] (2008) tested the multilineage potential of DPSCs in rat models. They found that these cell populations can help cardiac repair after myocardial infarction. The left coronary artery was ligated in an experimental rat model of acute myocardial infarction and the DPSCs were transplanted to the border of the infarction zone. After 4 weeks, the evidence of cardiac repair was noted by improved cardiac function, increase in the number of vessels, and a reduction in infarct size. DPSCs secrete different growth factors and cytokines such as vascular endothelial growth factor, insulin-like growth factor-1 and -2, and stem cell factor, which helped in inducing angiogenesis and cardiac regeneration at the infarction site. This finding reveals the potential of DPSCs to be used as an innovative and alternative approach for treatment of not only dental but also some other ischemic diseases.

Iohara et al. [73] (2008) demonstrated a novel stem cell source for vasculogenesis in ischemic conditions and isolated a highly vasculogenic side population of cells from porcine dental pulp. Nakashima et al. [74] (2009) observed that the CD31_/CD146_ SP expressed CD34 and VEGFR2 at similar levels to that expressed by EPCs and formed extensive networks of cords and tube-like structures on Matrigel. This experimentation in a mouse hind limb ischemia model revealed the neovascularization potential of human DPSCs. Bronckaers et al. [75] (2013) demonstrated that hDPSCs induced paracrine-mediated angiogenesis. Human DPSCs produced high amounts of angiogenic molecules, stimulated endothelial cell migration by activation of the P13l-AKT and MEK-ERK pathways, and significantly induced the formation of blood vessels in a chicken chorioallantoic membrane model. The authors provided an evidence of the suitability of DPSCs for treatment of pathologies correlated with inadequate angiogenesis such as stroke and MI.


   Dental Stem Cells and Endocrinology Top


The high-purity hepatic lineage differentiated from DPSCs in serum-free medium was referred to as hepatocyte-like cells (HLCs). [76] These stem cell-derived HLCs revealed their acquired hepatocyte functions such as glycogen storage and urea production. [77] Chen et al. [78] (2013) demonstrated hepatic-like differentiation of human DPSCs derived from cryopreserved dental pulp tissue from vital extracted teeth with disease. These differentiated cells demonstrated a polygonal shape and normal karyotype and expressed hepatic metabolic function genes and liver-specific genes. These cells revealed the properties of glycogen storage and urea production, indicating that their function was similar to normal HLCs. The use of cryopreserved tissue to generate HLCs offers a promising alternative for the treatment of liver diseases.

In diabetes, the autoimmune destruction of pancreatic β-cells or decreased sensitivity to insulin develops persistent hyperglycemia. In view of the limitations of conventional insulin-based therapy for diabetes, Bhonde et al. [79] (2013) suggested the use of differentiated stem cells or islet transplantation for replenishing the lost insulin-producing cells. The potential of DPSCs to differentiate into pancreatic cell lineage resembling islet-like cell aggregates (ICAs) was reported. [80] Carnevale et al. [81] (2013) reported that human DPSCs under appropriate stimuli express genes related to pancreatic β-cell development and function, including insulin and pancreatic and duodenal homebox-1. Recently, Kanafi et al. [82] (2013) demonstrated the transplantation of islet-like cell clusters (ICCs) derived from human DPSCs and SHEDs in diabetic mice. They noticed the reversal of hyperglycemia to the normal level in experimental diabetic mice. These observations suggested the use of dental pulp as an autologous stem cell therapy in diabetic patients.


   Dental Stem Cells and Future Perspectives Top


In regenerative dentistry, dentists should look for the repair of an edentulous area of a patient by regenerating or replacing new teeth. [83] The recognition of the dental source for stem cells could bring a new wave of revolution in regenerative medicine. An easy approach with minimum intervention required to retrieve dental connective tissues within the mouth offers a definite benefit and avoids refusal by recipients. Recent advances in the isolation methods and knowledge of DSCs have opened the doors of scientific research field to "regrow" lost dental structures. The popularity of research on stem cell therapy is mainly due to the extension of dental applications over other fields of medicine. [83] Current research efforts are revealing the potential of DSCs to differentiate into nondental tissues such as cardiac muscle. Untreatable diseases can be treated by implanting stem cells harvested from the teeth of affected individuals. The minimal intervention required to collect the stem cells and the absence of refusal issues may be valid reasons to apply such therapies in the near future. However, many in vitro and in vivo research studies have to be conducted before approving such therapeutic measures. Still, DSCs represent a powerful weapon holding a significant potential for future advancement in the area of regenerative dentistry and medicine. It is also important to have a concept of tooth banking for DSC preservation as a preventive therapy. This concept of tooth banking will be the future of the stem cell era.

 
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