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      NOTCH3 is expressed in human apical papilla and in subpopulations of stem cells isolated from the tissue


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          NOTCH plays a role in regulating stem cell function and fate decision. It is involved in tooth development and injury repair. Information regarding NOTCH expression in human dental root apical papilla (AP) and its residing stem cells (SCAP) is limited. Here we investigated the expression of NOTCH3, its ligand JAG1, and mesenchymal stem cell markers CD146 and STRO-1 in the AP or in the primary cultures of SCAP isolated from AP. Our in situ immunostaining showed that in the AP NOTCH3 and CD146 were co-expressed and associated with blood vessels having NOTCH3 located more peripherally. In cultured SCAP, NOTCH3 and JAG1 were co-expressed. Flow cytometry analysis showed that 7%, 16% and 98% of the isolated SCAP were positive for NOTCH3, STRO-1 and CD146, respectively with a rare 1.5% subpopulation of SCAP co-expressing all three markers. The expression level of NOTCH3 reduced when SCAP underwent osteogenic differentiation. Our findings are the first step towards defining the regulatory role of NOTCH3 in SCAP fate decision.

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          Most cited references18

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          The canonical Notch signaling pathway: unfolding the activation mechanism.

          Notch signaling regulates many aspects of metazoan development and tissue renewal. Accordingly, the misregulation or loss of Notch signaling underlies a wide range of human disorders, from developmental syndromes to adult-onset diseases and cancer. Notch signaling is remarkably robust in most tissues even though each Notch molecule is irreversibly activated by proteolysis and signals only once without amplification by secondary messenger cascades. In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection.
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            Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study.

            Mesenchymal stem cells (MSCs) have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells or DPSCs) and deciduous teeth (stem cells from human exfoliated deciduous teeth). We recently discovered another type of MSCs in the apical papilla of human immature permanent teeth termed stem cells from the apical papilla (SCAP). Here, we further characterized the apical papilla tissue and stem cell properties of SCAP using histologic, immunohistochemical, and immunocytofluorescent analyses. We found that the apical papilla is distinctive to the pulp in terms of containing less cellular and vascular components than those in the pulp. Cells in the apical papilla proliferated 2- to 3-fold greater than those in the pulp in organ cultures. Both SCAP and DPSCs were as potent in osteo/dentinogenic differentiation as MSCs from bone marrows, whereas they were weaker in adipogenic potential. The immunophenotype of SCAP is similar to that of DPSCs on the osteo/dentinogenic and growth factor receptor gene profiles. Double-staining experiments showed that STRO-1 coexpressed with dentinogenic markers such as bone sialophosphoprotein, osteocalcin, and growth factors FGFR1 and TGFbetaRI in cultured SCAP. Additionally, SCAP express a wide variety of neurogenic markers such as nestin and neurofilament M upon stimulation with a neurogenic medium. We conclude that SCAP are similar to DPSCs but a distinct source of potent dental stem/progenitor cells. Their implications in root development and apexogenesis are discussed.
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              The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering.

              Some clinical case reports have shown that immature permanent teeth with periradicular periodontitis or abscess can undergo apexogenesis after conservative endodontic treatment. A call for a paradigm shift and new protocol for the clinical management of these cases has been brought to attention. Concomitantly, a new population of mesenchymal stem cells residing in the apical papilla of permanent immature teeth recently has been discovered and was termed stem cells from the apical papilla (SCAP). These stem cells appear to be the source of odontoblasts that are responsible for the formation of root dentin. Conservation of these stem cells when treating immature teeth may allow continuous formation of the root to completion. This article reviews current findings on the isolation and characterization of these stem cells. The potential role of these stem cells in the following respects will be discussed: (1) their contribution in continued root maturation in endodontically treated immature teeth with periradicular periodontitis or abscess and (2) their potential utilization for pulp/dentin regeneration and bioroot engineering.

                Author and article information

                Genes Dis
                Genes Dis
                Genes & Diseases
                10 November 2015
                30 May 2015
                September 2015
                15 March 2016
                : 2
                : 3
                : 261-267
                [a ]Boston University, Henry M. Goldman School of Dental Medicine, Department of Endodontics, Boston, MA 02118, USA
                [b ]United Arab Emirates University, Department of Anatomy, Faculty of Medicine and Health Sciences, Al-Ain, United Arab Emirates
                [c ]University of Tennessee Health Science Center, College of Dentistry, Department of Bioscience Research, Memphis, TN 38163, USA
                Author notes
                [* ]Corresponding author. Cancer Research Building, University of Tennessee Health Science Center, 19 S. Manassas St. Lab Rm 225, Office 222, Memphis, TN 38163, USA. Tel.: +1 901 448 1490; fax: +1 901 448 3910

                Current address: Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, 875 Union Avenue, Memphis, TN 38163, USA.


                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).


                apical papilla,cd146,jag1,notch3,osteogenesis,scap,stemness,stro-1
                apical papilla, cd146, jag1, notch3, osteogenesis, scap, stemness, stro-1


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