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      Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers

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          Abstract

          Mesenchymal stem cell (MSC)-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations: CD51/CD140α, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells (DMSCs) from heterogeneous periodontal ligament cells (PDLCs). Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51 +/CD140α +, 0.8% were CD271 +, and 2.4% were STRO-1 +/CD146 +. Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271 + DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.

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          Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment.

          The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1 (a pivotal molecule of the HSC "niche" involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis.
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            Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine.

            To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.
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              Concise review: the surface markers and identity of human mesenchymal stem cells.

              The concept of mesenchymal stem cells (MSCs) is becoming increasingly obscure due to the recent findings of heterogeneous populations with different levels of stemness within MSCs isolated by traditional plastic adherence. MSCs were originally identified in bone marrow and later detected in many other tissues. Currently, no cloning based on single surface marker is capable of isolating cells that satisfy the minimal criteria of MSCs from various tissue environments. Markers that associate with the stemness of MSCs await to be elucidated. A number of candidate MSC surface markers or markers possibly related to their stemness have been brought forward so far, including Stro-1, SSEA-4, CD271, and CD146, yet there is a large difference in their expression in various sources of MSCs. The exact identity of MSCs in vivo is not yet clear, although reports have suggested they may have a fibroblastic or pericytic origin. In this review, we revisit the reported expression of surface molecules in MSCs from various sources, aiming to assess their potential as MSC markers and define the critical panel for future investigation. We also discuss the relationship of MSCs to fibroblasts and pericytes in an attempt to shed light on their identity in vivo. © 2014 AlphaMed Press.
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                Author and article information

                Journal
                Int J Oral Sci
                Int J Oral Sci
                International Journal of Oral Science
                Nature Publishing Group
                1674-2818
                2049-3169
                December 2015
                30 October 2015
                1 December 2015
                : 7
                : 4
                : 213-219
                Affiliations
                [1 ]Division of Oral Biology and Medicine, School of Dentistry, University of California at Los Angeles , Los Angeles, USA
                [2 ]Section of Orthodontics, School of Dentistry, University of California at Los Angeles , Los Angeles, USA
                Author notes
                [* ]Division of Oral Biology and Medicine, School of Dentistry, University of California at Los Angeles , CHS 63-014, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, USA E-mail: chong@ 123456dentistry.ucla.edu
                [* ]Division of Oral Biology and Medicine, School of Dentistry, University of California at Los Angeles , CHS 33-030, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, USA E-mail: cwang@ 123456dentistry.ucla.edu
                Article
                ijos201542
                10.1038/ijos.2015.42
                5153597
                26674423
                6e61f3c3-0ffc-4336-a670-85a2e7156d5f
                Copyright © 2015 West China School of Stomatology

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 17 September 2015
                Categories
                Original Article

                Dentistry
                cell surface markers,dental mesenchymal stem cells,periodontal ligament
                Dentistry
                cell surface markers, dental mesenchymal stem cells, periodontal ligament

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