Dental Papilla Research Articles

C-kit positive cells and networks in tooth germs of human midterm fetuses

Numerous studies have attempted to characterize the dental pulp stem cells. However, studies performed on prenatal human tissues have not been performed to evaluate the in situ characterization and topography of progenitor cells. We aimed to perform such a study using of antibodies for CD117/c-kit and multiplex antibody for Ki67+ caspase 3. Antibodies were applied on samples dissected from five human midterm fetuses. Positive CD117/c-kit labeling was found in mesenchymal derived tissues, such as the dental follicle and the dental papilla. The epithelial tissues, that is, dental lamina, enamel organ and oral epithelia, also displayed isolated progenitor cells which were CD117/c-kit positive. Interestingly, CD117/c-kit positive cells of mesenchymal derived tissues extended multiple prolongations building networks; the most consistent of such networks were those of the dental follicle and the perivascular networks of the dental papilla. However, the mantle of the dental papilla was also positive for CD117/c-kit positive stromal networks. The CD117/c-kit cell populations building networks appeared mostly with a Ki67 negative phenotype. The results suggest that CD117/c-kit progenitor cells of the prenatal tooth germ tissues might be involved in intercellular signaling.

Expression pattern of zinc-finger transcription factor Odd-skipped related 2 in murine development and neonatal stage

The Odd-skipped gene, first identified as a Drosophila pair-rule zinc-finger transcription factor, plays an important role in Drosophila development. The mammalian homolog, Odd-skipped related 2 (Osr2), regulates limb, tooth, and kidney development in mouse embryos. However, the detailed expression pattern of Osr2 during neonatal development remains unclear. In this study, we investigated Osr2 expression patterns in mouse neonatal and embryo tissues using qPCR and in situ hybridization methods. First, we examined the tissue distribution of Osr2 by qPCR, and found it to be highly expressed in the uterus and moderately in the testes, small intestine, and prostate. That expression was also found in eye, kidney, placenta, lung, thymus, lymph node, stomach, and skeletal muscle tissues, and in all embryonic stages. On the other hand, Osr2 was not expressed in brain, heart, liver, or spleen samples. Next, we examined the tissue localization of Osr2 using in situ hybridization. Osr2 was found in the craniofacial region on E13.5, with notable expression in dental germ mesenchyme as well as the renal corpuscle on E17.5. As for neonatal tissues, Osr2 was expressed in the dental papilla, dental follicle, Harderian gland, nasal bone, eyelid dermis, synovial joint, and tibial subcutis. Our findings suggest that Osr2 functions in reproductive system organs, such as the uterus, testes, prostate, placenta, and ovaries. Furthermore, based on its expression in kidney, Harderian gland, eyelid dermis, and tibial subcutis tissues, this transcription factor may be involved in hormone synthesis and function. Together, our results demonstrate the role of Osr2 in postnatal development and embryogenesis.

Induction of ankylosis in the incisor for orthodontic tooth movement in rats

The present research evaluated the induction of ankylosis and the eruption rate in rat incisors, with the aim of achieving stable anchorage for orthodontic tooth movement (OTM) of the molars. Fifteen male Wistar rats were used. In the Experimental group, the right superior incisor of each animal was extracted, denuded of the PDL and the dental papilla, and reimplanted. The Control group was the left superior incisors. The eruption rate was measured at 7, 10, 12, 14, and 16days after replantation. NiTi closed springs with a 50cN release force were installed for additional 9days, and the eruption rate was determined. Then, the rats were sacrificed, and ankylosis was examined by microscopic analysis. Differences with P<0.01 were defined as statistically significant. The eruption rates were 0 and 0.39mmday(-1) in the Experimental group and Control group, respectively. All incisors of the Experimental group showed ankylosis according to histological analysis. The methodology used to induce ankylosis in this study was effective for anchoring the incisors during the OTM of rat molars, eliminating the undesirable effects consequent to continuous eruption.

C-Jun N-Terminal Kinase (JNK) Mediates Wnt5a-Induced Cell Motility Dependent or Independent of RhoA Pathway in Human Dental Papilla Cells

Wnt5a plays an essential role in tissue development by regulating cell migration, though the molecular mechanisms are still not fully understood. Our study investigated the pathways involved in Wnt5a-dependent cell motility during the formation of dentin and pulp. Over-expression of Wnt5a promoted cell adhesion and formation of focal adhesion complexes (FACs) in human dental papilla cells (hDPCs), while inhibiting cell migration. Instead of activating the canonical Wnt signal pathway in hDPCs, Wnt5a stimulation induced activation of the JNK signal in a RhoA-dependent or independent manner. Inhibiting JNK abrogated Wnt5a-induced FACs formation but not cytoskeletal rearrangement. Both dominant negative RhoA (RhoA T19N) and constitutively active RhoA mutants (RhoA Q63L) blocked the Wnt5a-dependent changes in hDPCs adhesion, migration and cytoskeletal rearrangement here too, with the exception of the formation of FACs. Taken together, our study suggested that RhoA and JNK signaling have roles in mediating Wnt5a-dependent adhesion and migration in hDPCs, and the Wnt5a/JNK pathway acts both dependently and independently of the RhoA pathway.

Immortalized mouse dental papilla mesenchymal cells preserve odontoblastic phenotype and respond to bone morphogenetic protein 2

Odontogenesis is the result of the reciprocal interactions between epithelial–mesenchymal cells leading to terminally differentiated odontoblasts. This process from dental papilla mesenchymal cells to odontoblasts is regulated by a complex signaling pathway. When isolated from the developing tooth germs, odontoblasts quickly lose their potential to maintain the odontoblast-specific phenotype. Therefore, generation of an odontoblast-like cell line would be a good surrogate model for studying the dental mesenchymal cell differentiation into odontoblasts and the molecular events of dentin formation. In this study, immortalized dental papilla mesenchymal cell lines were generated from the first mouse mandibular molars at postnatal day 3 using pSV40. These transformed cells were characterized by RT-PCR, immunohistochemistry, Western blot, and analyzed for alkaline phosphatase activity and mineralization nodule formation. One of these immortalized cell lines, iMDP-3, displayed a high proliferation rate, but retained the genotypic and phenotypic characteristics similar to primary cells as determined by expression of tooth-specific markers and demonstrated the ability to differentiate and form mineralized nodules. Furthermore, iMDP-3 cells had high transfection efficiency as well as were inducible and responded to BMP2 stimulation. We conclude that the establishment of the stable murine dental papilla mesenchymal cell line might be used for studying the mechanisms of dental cell differentiation and dentin formation.

KLF4 promoted odontoblastic differentiation of mouse dental papilla cells via regulation of DMP1

Odontoblasts, which derive from dental papilla, are a type of terminally differentiated matrix-secreting cells. Previous studies have identified various transcription factors involved in the differentiation process of odontoblasts. We have recently found that Krüppel-like factor 4 (Klf4) was expressed in the polarizing and elongating odontoblasts, but the function of Klf4 in the differentiation of odontoblasts is still unclear. We hypothesized Klf4 promoted the differentiation of odontoblasts by up-regulating some odontoblast-related genes. In this study, we found that the expression of Klf4 increased significantly during the odontoblastic differentiation of primary mouse dental papilla cells and the mouse dental papilla cell line-mDPC6T. Overexpression of Klf4 significantly up-regulated odontoblast-related genes, such as Dmp1, Dspp, and Alp, and promoted the accumulation of mineral nodules. Knock-down of Klf4 down-regulated expression of Dmp1, Dspp, and Alp, and inhibited mineral deposition. We applied in silico analysis and identified one target gene of Klf4-Dmp1. Based on further analysis of ChIP data, EMSA and dual luciferase activity assays, we confirmed that Klf4 was able to specifically bind to the Dmp1 promoter and transactivate its expression. Furthermore, forced expression of Dmp1 in the Klf4 knock-down mDPC6T cell line significantly recovered its odontoblastic differentiation ability. Our data confirmed our hypothesis that Klf4 promotes the differentiation of odontoblasts via the up-regulation of Dmp1.

Effect of mineral trioxide aggregate on proliferation and differentiation of rat dental papilla cells

To investigate the effects of mineral trioxide aggregate(MTA) on the proliferation and differentiation of rat dental papilla cells(RDPC). RDPC were cultured by tissue block method and identified.RDPC of the third passage were cultured with material extract fluid containing different mass concentrations of MTA (0.002, 0.02,0.2, 2 and 20 g/L) for 3 d, those cultured with routine culture fluid served as control group. The proliferation-related parameters were measured by methyl thiazolyl tetrazolium(MTT) assay. RDPC were cultured with material extract fluids containing 0.002 g/L MTA, those cultured with routine culture fluid served as control group, the activity of alkaline phosphatase(ALP) at 1, 3,5, 7 d and the level of collagen I at 1, 3,5 d were detected. MTT results showed that the A value of RDPC of group 20 g/L (0.092 ± 0.011) was less than that of the control group (0.249 ± 0.006) at 3 d(P < 0.01), the A value of RDPC of group 0.02 g/L (0.267 ± 0.005) and 0.002 g/L (0.276 ± 0.006) were more than that of the control group (0.249 ± 0.006) at 3 d(P < 0.01). ALP detection proved that ALP activity of MTA at 3 d (0.217 ± 0.008), 5 d (0.253 ± 0.005) , 7 d (0.279 ± 0.004) were more than that of the control group at 3 d (0.166 ± 0.006) ,5 d (0.221 ± 0.006), 7 d (0.242 ± 0.004) (P < 0.01). Collagen I detection showed that the level of collagen I of MTA at 3 d[(78.46 ± 2.72) µg/L], 5 d[(90.73 ± 3.08) µg/L] were more than that of the control group at 3 d[ (66.75 ± 3.08) µg/L], [5 d (74.27 ± 3.50) µg/L] (P < 0.01). MTA of high concentrations can significantly inhibit cell growth, and of low concentrations can promote cells proliferation and differentiation.

Endodontic Retreatment of Dens Invaginatus Presenting with Gutta-Percha Overfilling at the Attached Gingiva and Chronic Apical Periodontitis: Unusual Clinical Report

This work describes the retreatment of an unusual case of dens invaginatus with gutta-percha overfilling at the gingival mucosa and chronic apical periodontitis in a 34-year-old woman. Initial periapical radiograph showed the presence of type II dens invaginatus with poor quality obturation, root perforation and chronic apical periodontitis of tooth 22. Dens invaginatus is a tooth malformation caused by infolding of the dental papilla during tooth development. This anomaly has been associated with increased prevalence of pulpal and periapical diseases. Conventional endodontic retreatment was performed using rotary files and calcium hydroxide paste as intracanal dressing. After 7 days, root canal was filled with guttapercha points and Sealapex® sealer. Obturation was radiographically followed and, after 3 years, absence of fistula and periapical radiolucency was observed, thus conventional endodontic therapy proved to be successful. Conventional endodontic retreatment of type II dens invaginatus has been successful for a 3-year period, showing a better treatment alternative. Conservative endodontic retreatment of dens invaginatus should be considered to promote periapical healing with complete reconstitution of bone and periodontal ligament regeneration without signs of recurrence over a period of 3 years. Moreover, it preserves the entire tooth.

Proliferation and osteo/odontoblastic differentiation of stem cells from dental apical papilla in mineralization‐inducing medium containing additional KH2PO4

Stem cells from the dental apical papilla (SCAPs) can be induced to differentiate along both osteoblast and odontoblast lineages. However, little knowledge is available concerning their differentiation efficiency in osteogenic media containing additional KH2 PO4 . Stem cells from the dental apical papilla were isolated from apical papillae of immature third molars and treated with two kinds of mineralization-inducing media, MM1 and MM2, differing in KH2 PO4 concentration. Proliferation and osteo/odontogenic differentiation capacity of MM1/MM2-treated SCAPs were investigated and compared both in vitro and in vivo. Cell counting and flow cytometry demonstrated that MM2 containing 1.8 mm additional KH2 PO4 significantly enhanced proliferative potential of SCAPs, compared to MM1. Osteo/odontogenic capacity of SCAPs was much better in MM2 medium than in MM1, as indicated by elevated alkaline phosphatase activity, increased calcium deposition and upregulated expression of osteo/odontoblast-specific genes/proteins (for example, runt-related transcription factor 2, osterix, osteocalcin, dentin sialoprotein, and dentin sialophosphoprotein). In vivo transplantation findings proved that SCAPs in MM2 group generated more mineralized tissues, and presented higher expression of osteo/odontoblast-specific proteins (osteocalcin and dentin sialoprotein) than those in the MM1 group. Mineralization-inducing media supplemented with 1.8 mm additional KH2 PO4 significantly enhanced cell proliferation and improved differentiation capacity of SCAPs along osteo/odontogenic cell lineages, compared to counterparts lacking additional KH2 PO4 .

MiR-145 and miR-143 Regulate Odontoblast Differentiation through Targeting Klf4 and Osx Genes in a Feedback Loop

Dentin tissue is derived from mesenchymal cells induced into the odontoblast lineage. The differentiation of odontoblasts is a complex process regulated by several transcriptional factor signaling transduction pathways. However, post-translational regulation of these factors during dentinogenesis remains unclear. To further explore the mechanisms, we investigated the role of microRNA (miRNA) during odontoblast differentiation. We profiled the miRNA expression pattern during mouse odontoblast differentiation using a microarray assay and identified that miR-145 and miR-143 were down-regulated during this process. In situ hybridization verified that the two miRNAs were gradually decreased during mouse odontoblast differentiation. Loss-of-function and gain-of-function experiments revealed that down-regulation of miR-145 and miR-143 could promote odontoblast differentiation and increased Dspp and Dmp1 expression in mouse primary dental pulp cells and vice versa. We found that miR-145 and miR-143 controlled odontoblast differentiation through several mechanisms. First, KLF4 and OSX bind to their motifs in Dspp and Dmp1 gene promoters and up-regulate their transcription thereby inducing odontoblast differentiation. The miR-145 binds to the 3'-UTRs of Klf4 and Osx genes, inhibiting their expression. Second, KLF4 repressed miR-143 transcription by binding to its motifs in miR-143 regulatory regions as detected by ChIP assay and dual luciferase reporter assay. Third, miR-143 regulates odontoblast differentiation in part through miR-145 pathway. Taken together, we for the first time showed that the miR-143 and miR-145 controlled odontoblast differentiation and dentin formation through KLF4 and OSX transcriptional factor signaling pathways.

N-cadherin is Required for Cytodifferentiation during Zebrafish Odontogenesis

N-cadherin is a well-studied classic cadherin involved in multiple developmental processes and is also known to have a signaling function. Using the zebrafish (Danio rerio) as a model, we tested the hypothesis that tooth morphogenesis is accompanied by dynamic changes in N-cadherin distribution and that absence of N-cadherin disturbs tooth development. N-cadherin, encoded by the gene cdh2, is absent during the initiation and morphogenesis stages of both primary (first-generation) and replacement teeth, as demonstrated by immunohistochemistry. However, N-cadherin is up-regulated at the onset of differentiation of cells of the inner dental epithelium and the dental papilla, i.e., the ameloblasts and odontoblasts, respectively. In the inner dental epithelium, N-cadherin is co-expressed with E-cadherin, excluding the occurrence of cadherin switching such as observed during human tooth development. While early lethality of N-cadherin knockout mice prevents any functional study of N-cadherin in mouse odontogenesis, zebrafish parachute (pac) mutants, deficient for N-cadherin, survive beyond the age when primary teeth normally start to form. In these mutants, the first tooth forms, but its development stops at the early cytodifferentiation stage. N-cadherin deficiency also completely inhibits the development of the other first-generation teeth, possibly due to the absence of N-cadherin signaling once the first tooth has differentiated.

Establishment and characterization of a tamoxifen-mediated reversible immortalized mouse dental papilla cell line

Odontoblasts are a type of non-proliferating and terminally differentiated cells that play an important role in the pulpo-dentinal complex. Mouse dental papilla cells (mDPCs), which can differentiate into odontoblast-like cells in vitro, have a limited life span. We combined the traditional strategy of "Cre/LoxP-based reversible immortalization" with a tamoxifen-regulated Cre recombination system to generate a tamoxifen-mediated reversibly immortalized mouse dental papilla cell line, mDPCET. mDPCs were sequentially transduced with a floxed SV40 T antigen-TK (SV40Tag-TK) and an (ERT2)Cre(ERT2)-expressing plasmid. Clonal-isolated SV40Tag- and Cre-positive cells showed modified growth characteristics and a significantly extended life span. When mDPCET cells were treated with 4-hydroxytamoxifen, (ERT2)Cre(ERT2) translocated from the cytoplasm to the nucleus and caused the excision of SV40Tag-TK, which led to the reversion of mDPCETs. After the immortalization was reversed, the cells underwent replicative senescence and transitioned into a more differentiated state. Tamoxifen-mediated reversible immortalization, therefore, allows for the expansion of primary mDPCs, leads to the production of odontoblast-like cells that retain most odontoblast-specific properties, and can represent a safe and ready-to-use method due to its simple manipulation.

Bilateral radicular dens in dente in mandibular premolars

Dens invaginatus (DI) is a rare developmental anomaly that results from an invagination of the enamel organ into the dental papilla during odontogenesis. The invagination ranges from a slight pitting (coronal type) to an anomaly occupying most of the crown and root (radicular type). Radicular DI is an unusual dental anomaly. Although a clinical examination may reveal a deep fissure or pit on tooth surface, but radiographic examination is the most realistic way to diagnose the invagination. The objective of this case presentation is to report a rare case of radicular dens invaginatus bilaterally in mandibular premolars.

Dental Pulp Stem Cells: A Promising Tool for Tissue Regeneration

Stem cells are the master cells of our body that act as building block to regenerate and turn into cells that form tissues, organs and systems in the human body. Several loci '' or within the adult human body are colonised by a significant number of stem cells. However, access to these potential collection sites often is a limiting point. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The interaction with biomaterials is a further point that needs to be considered for the therapeutic use of stem cells. Dental pulp stem cells (DPSCs) have been demonstrated to answer all of these issues: access to the collection site of these cells is easy and produces very low morbidity; extraction of stem cells from pulp tissue is highly efficient; they have an extensive differentiation ability; and the demonstrated interactivity with biomaterials makes them ideal for tissue reconstruction. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp,periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration. This review describes about different sources of stem cells eg human embryonic stem cells (ES) cells , somatic or adult stem cells , stem cells of Dental tissue origin and induced pluripotent stem cells and their characteristic and new findings in the field of dental stem cell research and on their potential use in the tissue regeneration.

An Unusual Type II Dens Invaginatus with Calcified Canals in a Maxillary Lateral Incisor – A Case Report

Dens invaginatus is a developmental malformation resulting from the invagination of enamel organ into the dental papilla. Management of dens invaginatus is an endodontic challenge. Presence of calcified canals in dens invaginatus makes it even more complicated. Modification of the treatment plan is required to treat such cases. This case report deals with the management of a Type II Dens Invaginatus in a lateral incisor with calcified canals.

Papilliferous Keratoameloblastoma: An Extremely Rare Case Report

Odontogenic tumors develop in the jaw bones from the odontogenic tissue-oral epithelium in tooth germ, enamel organ, dental papilla, reduced enamel epithelium, remnants of Hertwig's root sheath or dental lamina, and so forth. Hence, a bewildering variety of tumors are encountered in the maxilla and mandible. Ameloblastoma is the second most common odontogenic neoplasm after odontomes, and it has numerous clinical and histologic variants. We report a very rare histologic variant: the papilliferous keratoameloblastoma which is the fifth reported case in the English literature.

Apexification with white MTA in an immature permanent tooth with dens invaginatus

Dens invaginatus, also known as “dens in dente”, is a developmental dental anomaly resulting in an invagination of the enamel organ into the dental papilla. These cases present technical difficulties to the root canal treatment. Apexification using an apical plug of mineral trioxide aggregate (MTA) has been indicated as an alternative to long-term intracanal use of calcium hydroxide in immature permanent teeth. It is considered as a simple and rapid technique. This paper reports a case of Oehlers’ Type 1 dens invaginatus in an immature permanent maxillary right lateral incisor, which presented pulp necrosis secondary to dental trauma and was treated by apexification with white MTA apical plugging followed by conventional root canal therapy. The operative procedures are described and the technique is discussed. The physical and biological properties of MTA, associated with appropriate instrumentation and obturation techniques, make this material an excellent option in the endodontic therapy of immature permanent teeth with dens invaginatus.

Magnetic resonance imaging findings in Axenfeld&amp;ndash;Rieger syndrome

Axenfeld–Rieger syndrome (ARS) is a genetic disorder representing a disease spectrum resulting from neural crest cell maldevelopment. Glaucoma is a common complication from the incomplete formation of the iridocorneal angle structures. Neural crest cells also form structures of the forebrain and pituitary gland, dental papillae, aortic arch walls, genitalia, and long bones; therefore, patients with ARS manifest a wide range of systemic findings. To our knowledge, detailed magnetic resonance imaging findings have not been previously reported. We report a case of a 19-month-old Indian male diagnosed with ARS with emphasis on magnetic resonance imaging findings of the globes, brain, teeth, and skull base.

Dental tissues as adult stem cell source

Multipotent stem cells are the most crucial factor in tissue engineered regeneration procedures. Although bone marrow has been most widely studied and used as mesenchymal stem cell (MSC) source, several attempts have recently been made to obtain multipotential stem cells from more easily accessible sources, including skin, fat, periosteum and dental tissues1-5. In previous studies, skin has been shown as an excellent adult stem cell source, which differentiated into osteogenic and neural cells in vitro and enhanced bone formation in the maxillary sinus floor and nerve regeneration in vivo5,6. Further, stem cells derived from fetus differentiated into primordial germ cell and oocyte, and exhibited similar characteristics compared to embryonic stem cells7,8. However, harvesting skin tissue also involves an invasive procedure, and stem cells from the skin of older donors possess less stemness and regenerative potential than that of younger donors4,5. Dental tissues from extracted teeth could be used as alternative sources of adult stem cells. Dental stem cells were firstly isolated from the pulp tissues of removed third molars (dental pulp stem cell, DPSC), and showed similar characteristics with bone marrow derived MSC1,2. After then, some researchers have succeeded in the isolation of stem cells from the pulp tissues of human exfoliated deciduous teeth (SHED)9 or mesiodens10. Subsequently, other dental tissues, such as periodontal ligament11, root apical papilla12, and tooth follicle13, have been explored as adult stem cell sources. MSC-like characteristics of dental stem cells with plastic adherent growth and colony formation, expression of MSC-specific cell surface markers, and multilineage in vitro differentiation ability were similar to those of MSCs from skin or bone marrow14. However, interestingly, different dental tissues from same donor showed varying stem cell characteristics, including transcription factor expression levels and in vitro differentiation potential15. Stem cells from root papilla showed the highest expression level of transcription factors and cell surface markers15. However, dental follicle derived cells showed enhanced osteoblast-specific genes and ectopic bone formation after in vivo transplantation14, indicating dental follicle is the powerful stem cell source in bone tissue regeneration. Dental pulp is expected to harbor the pools of undifferentiated precursor cells for nerve or vascular tissue regeneration. The most powerful advantage of dental tissues as stem cells source is that primitive and multipotent tissues could be obtained around age 20, a later age compared to that of other stem cell sources, such as umbilical cord blood or matrix. If these dental tissues are preserved for long time without losing their stemness, they could be used as autologous stem cell source for demanding applications in regenerative medicine. A recent study reported the successful isolation of stem cells from long-term cryopreserved dental pulp tissues of deciduous teeth using a cryoprotectant, 90% fetal bovine serum (FBS) and 10% dimethyl sulfoxide16. However, FBS is xenogenic material for human tissue and cells and may alter tissue's properties, and not suitable for long-term preservation of human tissues. Interestingly, an efficient and safe dental tissue cryopreservation method using sucrose and ethylene glycol has been developed, and further analyses are being proceeded for its clinical application (data not published). In near future, the dental tissues, follicle, pulp and root papilla, of extracted wisdom teeth could be cryopreserved for later use as autologous stem cells sources.

Modulation of osteoblastic/odontoblastic differentiation of adult mesenchymal stem cells through gene introduction: a brief review

Bone tissue engineering is one of the important therapeutic approaches to the regeneration of bones in the entire field of regeneration medicine. Mesenchymal stem cells (MSCs) are actively discussed as material for bone tissue engineering due to their ability to differentiate into autologous bone. MSCs are able to differentiate into different lineages: osteo/odontogenic, adipogenic, and neurogenic. The tissue of origin for MSCs defines them as bone marrow-derived stem cells, adipose tissue-derived stem cells, and, among many others, dental stem cells. According to the tissue of origin, DSCs are further stratified into dental pulp stem cells, periodontal ligament stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, and dental papilla cells. There are numerous in vitro/in vivo reports suggesting successful mineralization potential or osteo/odontogenic ability of MSCs. Still, there is further need for the optimization of MSCs-based tissue engineering methods, and the introduction of genes related to osteo/odontogenic differentiation into MSCs might aid in the process. In this review, articles that reported enhanced osteo/odontogenic differentiation with gene introduction into MSCs will be discussed to provide a background for successful bone tissue engineering using MSCs with artificially introduced genes.