The role of cell surface markers and enamel matrix derivatives on human periodontal ligament mesenchymal progenitor responses in vitro

Faculty of Odontology, University Paul-Sabatier, 3 Chemin des Maraîchers, 31062 Toulouse Cedex, France.
Biomaterials (Impact Factor: 8.56). 10/2011; 32(30):7375-88. DOI: 10.1016/j.biomaterials.2011.06.043
Source: PubMed

ABSTRACT Periodontitis is a chronic-, infectious-disease of the human periodontium that is characterized by the loss of supporting tissues surrounding the tooth such as the periodontal ligament (PDL), cementum and alveolar bone. Regeneration of the periodontium is dependent on the participation of mesenchymal stem/stromal cells (MSC) resident in the PDL. Enamel matrix derivative (EMD), an extract from immature porcine enamel rich in amelogenin protein but that also contain bone morphogenetic protein (BMP), is used to treat periodontal defects. The effects of EMD on MSC cells of the PDL are not well characterized. In this in vitro study, we identify PDL progenitor cells from multiple individuals and demonstrate that EMD stimulates them. We show that the effect of EMD on cell proliferation and migration is mediated through the amelogenin it contains, while the differentiation of these progenitor cells to cell types of mineralized tissue is mainly due to BMP signaling.

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    • "The anabolic potential of EMD is well-documented [49,50,51,52] and used extensively in regenerative periodontal treatment. When EMD was used alone at concentrations ranging from 15 to 75 µg/mL it stimulated DHT synthesis in osteoblasts with 14C-T as substrate. "
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    ABSTRACT: Our study seeks to explore anabolic effects of a periodontal regenerative agent enamel matrix derivative (EMD). Its modulation by nicotine and the anti-oxidant glutathione (GSH) are investigated in human periosteal fibroblasts (HPF) and MG63 osteoblasts. Androgen biomarkers of oxidative stress and healing, resulting from radiolabeled androgen substrates are assayed. This in vitro model simulates a redox environment relevant to the periodontal lesion. It aims to confirm the hypothesis that EMD is an effective regenerative agent in a typically redox environment of the periodontal lesion. Monolayer cultures of MG63 osteoblasts and HPF established in culture medium are incubated with androgen substrates, and optimal concentrations of EMD, nicotine and GSH, alone and in combination. EMD significantly enhances yields of 5α-dihydrotestosterone (DHT) an effective bioactive metabolite, alone and in combination with GSH, to overcome oxidative effects of nicotine across cultures. The 'in vitro' findings of this study could be extrapolated to "in vivo" applications of EMD as an adjunctive regenerative therapeutic agent in an environment of chronic inflammation and oxidative stress. Increased yields of DHT implicated in matrix synthesis and direct antioxidant capacity, confirm the potential applications for enamel matrix derivative in periodontal regenerative procedures.
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    ABSTRACT: Mesenchymal stromal cells (MSCs) and their precursor cells (MPCs) can proliferate and differentiate into multiple mesodermal and some ectodermal and endodermal tissues. Culture-expanded MSCs are currently being evaluated as a possible cell therapy to replace/repair injured or diseased tissues. While a number of mAb reagents with specificity to human MSCs, including STRO-1, STRO-3 (BLK ALP), CD71 (SH2, SH3), CD106 (VCAM-1), CD166, and CD271, have facilitated the isolation of purified populations of human MSCs from primary tissues, few if any mAb reagents have been described that can be used to isolate equivalent cells from other species. This is of particular relevance when assessing the tissue regenerative efficacy of MSCs in large immunocompetent, preclinical animal models of disease. In light of this, we sought to generate novel monoclonal antibodies (mAb) with specific reactivity against a cell surface molecule that is expressed at high levels by MSCs from different species. Using CD106 (VCAM-1)-selected ovine MSCs as an immunogen, mAb-producing hybridomas were selected for their reactivity to both human and ovine MSCs. One such hybridoma, termed STRO-4, produced an IgG mAb that reacted with <5% of human and ovine bone marrow (BM) mononuclear cells. As a single selection reagent, STRO-4 mAb was able to enrich colony-forming fibroblasts (CFU-F) in both human and ovine BM by 16- and 8-folds, respectively. Cells isolated with STRO-4 exhibited reactivity with markers commonly associated with MSCs isolated by plastic adherence including CD29, CD44, and CD166. Moreover, when placed in inductive culture conditions in vitro, STRO-4(+) MSCs exhibited multilineage differentiation potential and were capable of forming a mineralized matrix, lipid-filled adipocytes, and chondrocytes capable of forming a glycosaminoglycan-rich matrix. Biochemical analysis revealed that STRO-4 identified the beta isoform of heat shock protein-90 (Hsp90beta). In addition to identifying an antibody reagent that identifies a highly conserved epitope expressed by MSCs from different species, our study also points to a potential role for Hsp90beta in MSC biology.
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    ABSTRACT: The use of biomaterials in dentistry is more widespread than in any other medical field in terms of both amount and variety. Most of them were not originally designed for dental applications but for other medical applications or, sometimes, for no medical purposes. Among these materials, biodegradable materials play an important role, especially in bone regeneration and in periodontal surgery. This paper briefly reviews some degradable polymers developed as tools for the treatment of periodontal and bone diseases. We discuss materials previously applied in other industrials contexts, such as polyesters, methylcellulose, and chitosan and we provide perspectives for their use in periodontal regeneration.
    Journal of applied biomaterials & biomechanics (JABB) 12/2011; 9(3):223-31. DOI:10.5301/JABB.2011.8867 · 1.16 Impact Factor
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