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  <front>
    <journal-meta id="journal-meta-1">
      <journal-id journal-id-type="nlm-ta">Innovative Journal</journal-id>
      <journal-id journal-id-type="publisher-id">Innovative Journal</journal-id>
      <journal-id journal-id-type="journal_submission_guidelines">http://jmbas.in/index.php/jmbas</journal-id>
      <journal-title-group>
        <journal-title>Journal of Medical Biomedical and Applied Sciences</journal-title>
      </journal-title-group>
      <publisher>
        <publisher-name>Innovative Journal</publisher-name>
      </publisher>
      <issn>2589-8779</issn>
    </journal-meta>
    <article-meta id="article-meta-1">
      <title-group>
        <article-title id="at-c88895473154">The Potency of Dental Mesenchymal Stem Cells: A Short Review of the Literature</article-title>
      </title-group>
      <contrib-group>
        <contrib id="c-461938b54e19" corresp="yes">
          <name id="n-fb3590d97128">
            <surname>Miteva</surname>
            <given-names>Marina</given-names>
          </name>
          <email>mia9580@yahoo.com</email>
          <xref id="x-fd00c3bf2322" rid="a-eb219b40a96f" ref-type="aff">1</xref>
        </contrib>
        <aff id="a-eb219b40a96f">
          <institution>Faculty of Dental Medicine, Medical University-Sofia, Bulgaria</institution>
          <addr-line></addr-line>
        </aff>
      </contrib-group>
      <pub-date>
        <day>19</day>
        <month>8</month>
        <year>2019</year>
      </pub-date>
      <permissions>
        <copyright-statement>Copyright</copyright-statement>
        <copyright-year>2019</copyright-year>
      </permissions>
      <abstract id="abstract-c4ed31fb41b1">
        <title id="abstract-title-f0a284d7ee50">Abstract:</title>
        <p id="t-71e234590a7b">There is a pool of nondifferentiated mesenchymal stem cells (MSC) in human dental tissues. These cells are capable in appropriate conditions to differentiate into various cell types. Dental MSC are ideal candidates for stem cell regenerative therapy. However, further research is required before their routine application in the clinical practice. </p>
        <p id="p-f6e70717fa9b"/>
      </abstract>
      <kwd-group id="kwd-group-1">
        <title>Keywords</title>
        <kwd>Dental Stem Cells</kwd>
        <kwd>Stem Cell Differentiation</kwd>
        <kwd>Stem Cell Markers</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title id="t-873807836359">Introduction:</title>
      <p id="t-bbe83eb74c57">Nondifferentiated stem cells are known to be presented all over the human body. Dental structures represent a promising source of stem cells due to the easy access and lack of legal considerations about the biomaterials collection. Nowadays, several different types of dental mesenchymal stem cells (MSC) have been isolated and thorough investigation of their properties has been carried out <xref id="x-50280f2ef733" rid="R56971313141811" ref-type="bibr">1</xref>. These are stem cells from dental pulp of permanent teeth (DPSC-dental pulp stem cells) and temporary teeth (SHED-stem cells from human exfoliated deciduous teeth), periodontal ligament stem cells (PDLSC), stem cells from apical papilla (SCAP) and stem cells from pericoronal follicular tissues (DFSC-dental follicle stem cells)<xref rid="R56971313141811" ref-type="bibr">1</xref>,<xref rid="R56971313141853" ref-type="bibr">2</xref>. All of them are capable of self-renewal, colonogenicity and multilineage differentiation <xref rid="R56971313141853" ref-type="bibr">2</xref>,<xref rid="R56971313141854" ref-type="bibr">3</xref>.</p>
      <p id="p-488adbec86dd"> - DPSC - were first isolated in 2000 by Gronthos et al. <xref id="x-9a86f39c2d1b" rid="R56971313141855" ref-type="bibr">4</xref>  from dental pulp of intact third molars. These cells are able to differentiate into odontoblast-like cells and to regenerate the pulp-dentine complex after implantation in immunocompromised mice <xref id="x-bd1efdf09547" rid="R56971313141855" ref-type="bibr">4</xref>. DPSC have properties quite similar to bone marrow mesenchymal stem cells (BMSC). Аappropriate <italic id="emphasis-1">in vitro</italic> conditions significantly affect their phenotype <xref id="x-5d16b3f1e71c" rid="R56971313141856" ref-type="bibr">5</xref>.</p>
      <p id="p-fe97a75a2a49"> - SHED are found in dental pulp of deciduous teeth with advanced root resorption<xref id="x-0f53835090c5" rid="R56971313141857" ref-type="bibr">6</xref>. Stem cells with positive expression of wide range markers have been identified in the pulp of deciduous teeth, revealing the presence of heterogenic cell population <xref id="x-1384ac541ee9" rid="R56971313141858" ref-type="bibr">7</xref>. SHED can differentiate to osteoblast-like and are able to initiate the formation of a bone-like matrix <xref id="x-9c25714846cb" rid="R56971313141857" ref-type="bibr">6</xref>. </p>
      <p id="p-599bfc001c4a"> - PDLSC have been first isolated in 2004 by Seo et al. <xref id="x-acebfd4c41a2" rid="R56971313141859" ref-type="bibr">8</xref>. They have all the characteristics of stem cells and are able to differentiate into adipocytes, osteoblast-like cells and to form cementum-periodontal ligament-like complex in immunocompromised mice <xref id="x-e4c3bd1dbc9f" rid="R56971313141859" ref-type="bibr">8</xref>. PDLSC are collected from the root surface of the extracted teeth, as well as from the dental socket wall. According to Wang et al. <xref id="x-4bf4c3dd59d8" rid="R56971313141860" ref-type="bibr">9</xref>  these two types of cells vary in their differentiation potential, as cells isolated from the walls of the bone socket can lead to better regeneration of the alveolar bone compared to cells from the root surface. Various active molecules and growth factors are capable to modify their stem cell properties<xref rid="R56971313141861" ref-type="bibr">10</xref>,<xref rid="R56971313141862" ref-type="bibr">11</xref>,<xref rid="R56971313141863" ref-type="bibr">12</xref>,<xref rid="R56971313141864" ref-type="bibr">13</xref>. </p>
      <p id="p-d7c9698f1e0d"> - SCAP are isolated from the apical papilla situated on the root apices of developing teeth <xref id="x-e9aaa9a36d91" rid="R56971313141865" ref-type="bibr">14</xref>. They have a high potential of proliferation and differentiation into odontoblast-like cells, as they originate from nonmature dental structures that are still at very early stage of development <xref id="x-b0c097a8e7fd" rid="R56971313141865" ref-type="bibr">14</xref>.</p>
      <p id="p-55957627f677"> - DFSC - The dental follicle is a sac that surrounds the tooth germ until the tooth has fully erupted. Precursor cells capable of differentiating into cementoblasts, osteoblasts and periodontal ligament cells have been isolated from human dental follicle <xref id="x-32ff5bad4adc" rid="R56971313141866" ref-type="bibr">15</xref>.</p>
    </sec>
    <sec>
      <title id="t-5f580f7bda01">Regenerative Potential of Dental Mesenchymal Stem Cells:</title>
      <p id="t-fee79ff42be9">In the past years, there have been increasing number of reports revealing the potential application of MSCs in the clinical practice <xref rid="R56971313141867" ref-type="bibr">16</xref>,<xref rid="R56971313141868" ref-type="bibr">17</xref>. Cells isolated from dental tissues are a heterogeneous cell population consisting of stem/progenitor cells, fibroblasts, etc.<xref rid="R56971313141857" ref-type="bibr">6</xref>,<xref rid="R56971313141869" ref-type="bibr">18</xref>. Isolation of primary stem cell cultures, followed by thorough characterization and investigation of their properties would lead to more predictable results of their <italic id="e-47c8c8c07e0e">in vivo</italic> application.</p>
      <p id="p-b893705a5048"> According to some authors, dental MSC have different ability of <italic id="emphasis-2">de novo</italic> tissues and structures formation <xref id="x-7dc4e871f61e" rid="R56971313141870" ref-type="bibr">19</xref>. DPSC, SHED and SCAP have the potential to initiate bone, cartilage, and pulpodentin complex regeneration, while PDLSC stimulate formation and regeneration of muscle tissue, tendons, and ligaments <xref id="x-4b7c093551d3" rid="R56971313141870" ref-type="bibr">19</xref>. The ability of dental MSCs of bone regeneration makes them ideal candidated in the complex management of extensive periodontal bone defects. Their potential to differentiate into bone-like cells and to synthesize a bone matrix has been widely investigated<xref id="x-d46744f31d33" rid="R56971313141855" ref-type="bibr">4</xref> <xref id="x-791c4d97f5e5" rid="R56971313141859" ref-type="bibr">8</xref>.</p>
      <p id="p-7b0adaf63ad0"> Regenerative osteogenic potential of dental MSC can be investigated <italic id="emphasis-3">in vitro</italic> after the addition of suitable active molecules in the cell culture media that can induce osteogenic differentiation. Wide number of studies report strong Alizarin red in MSC when cultivated in osteogenic differentiation media <xref rid="R56971313141855" ref-type="bibr">4</xref>,<xref rid="R56971313141859" ref-type="bibr">8</xref>. Other methods, like flow-cytometry markers expression also reveal specific differentiation ability in stem cells <xref id="x-68e716f16952" rid="R56971313141871" ref-type="bibr">20</xref>. The addition of active substances such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) bone morphogenetic protein-bone morphogenetic protein (BMP), etc., in the cell culture media <italic id="emphasis-4">in vitro</italic>, affects significantly the differentiation processes<xref rid="R56971313141872" ref-type="bibr">21</xref>,<xref rid="R56971313141873" ref-type="bibr">22</xref>,<xref rid="R56971313141874" ref-type="bibr">23</xref>. BMP family have positive effect on osteogenesis<xref rid="R56971313141872" ref-type="bibr">21</xref>,<xref rid="R56971313141874" ref-type="bibr">23</xref>. There is already evidence in the literature of <italic id="emphasis-5">in vivo</italic> experiments that demonstrate the ability of BMP to stimulate bone regeneration in peri-implant tissues<xref id="x-516fb80aa80f" rid="R56971313141875" ref-type="bibr">24</xref>. Lee et al.<xref id="x-b9b2767986d1" rid="R56971313141875" ref-type="bibr">24</xref> report that VEGF stimulates the mineralization of PDL cells, whereas cell cultivation with FGF-2 has an inhibitory effect on the osteogenesis. Each growth factor is having different effects on cells <xref id="x-6b3c45495f9e" rid="R56971313141876" ref-type="bibr">25</xref>. Studies about the effects of growth factors on stem cells would contribute to their introduction in the clinic for the treatment of wide number pathological conditions associated with soft tissue destruction and bone resorption. </p>
      <p id="p-f3865c1ad2c5"> Although the functions of dental MSCs are well described in the literature <xref rid="R56971313141853" ref-type="bibr">2</xref>,<xref rid="R56971313141855" ref-type="bibr">4</xref>, reports about their effect in patients <italic id="emphasis-6">in vivo</italic> are still scarce. The goal of all MSC studies is their further successful clinical application. Conduction of well-planned experiments, revealing in detaisl the optimal conditions for their proper functioning is needed <xref id="x-53a8d1f834a1" rid="R56971313141870" ref-type="bibr">19</xref>. </p>
    </sec>
    <sec>
      <title id="t-9b89bfa77591">Conclusion: </title>
      <p id="t-02b883249af9">MSC with high potential have been isolated from human dental tissues. However, little is known about their regenerative potential <italic id="e-4185d1c5826d">in vivo</italic> due to the lack of sufficient scientific data about their application in clinical trials. Further research is needed to clarify the effects of various molecules on dental MSC and to reveal the most appropriate conditions of stem cell therapy</p>
      <p id="p-3d09c248ccfe"/>
      <p id="p-42c634f1c2bd"> </p>
      <p id="paragraph-9de74b29f282"> </p>
      <p id="p-87142457489d"/>
    </sec>
  </body>
  <back>
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