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      Autologous dental pulp mesenchymal stem cells for inferior third molar post-extraction socket healing: A split-mouth randomised clinical trial

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          Abstract

          Background

          Since the discovery of adult mesenchymal stem cells extensive research has been conducted to determine their mechanisms of differentiation and effectiveness in cell therapy and regenerative medicine.

          Material and Methods

          To assess the efficacy of autologous dental pulp mesenchymal stem cells delivered in a collagen matrix for post-extraction socket healing, a single-centre, double-blind, randomised, split-mouth, controlled clinical trial was performed. Both impacted mandibular third molars were extracted from 32 patients. Dental pulp was collected and dissociated; the resulting cell suspension, obtained by centrifugation, was incorporated into a resorbable collagen matrix and implanted in 32 experimental post-extraction sockets. Collagen matrices alone were implanted in 32 contralateral, control post-extraction sockets. Two neuroradiologists independently assessed the extent of bone repair at 6 months after the extractions. Computed tomography (CT, Philips Brilliance) and an advanced display platform (IntelliSpace Portal) was used to record extraction socket density, expressed as Hounsfield units (HU) and height (mm) of the distal interdental bone septum of the second molar. Measurements at 6 months post-extraction were compared with measurements obtained immediately after extraction. Data were analysed with the statistical program STATA 14.

          Results

          Two patients dropped out of the study. The final sample consisted of 22 women and 8 men (mean age, 23 years; range: 18–30 years). Clinical, radiological, and surgical characteristics of impacted third molars of the control and experimental groups were homogeneous. Measurements obtained by the two neuroradiologists showed agreement. No significant differences were found in the extent of bone repair during analyses of density ( p=0.4203 neuroradiologist 1; p=0.2525 neuroradiologist 2) or interdental septum height ( p=0.2280 neuroradiologist 1; p=0.4784 neuroradiologist 2).

          Conclusions

          In our clinical trial, we were unable to demonstrate that autologous dental pulp mesenchymal stem cells reduce socket bone resorption after inferior third molar extraction.

          Key words:Clinical trial, autologous, pulpal stem cells, extraction socket healing.

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          Most cited references14

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          Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12-month prospective study.

          Preservation of alveolar bone volume following tooth extraction facilitates subsequent placement of dental implants and leads to an improved esthetic and functional prosthodontic result. The aim of the present study was to assess bone formation in the alveolus and the contour changes of the alveolar process following tooth extraction. The tissue changes after removal of a premolar or molar in 46 patients were evaluated in a 12-month period by means of measurements on study casts, linear radiographic analyses, and subtraction radiography. The results demonstrated that major changes of an extraction site occurred during 1 year after tooth extraction.
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            Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation.

            Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiation in vitro and in vivo. We previously reported that SBP-DPSCs are multipotent stem cells able to differentiate into osteoblasts, which synthesize three-dimensional woven bone tissue chips in vitro. In this study, we followed the temporal expression pattern of specific markers in SBP-DPSCs and found that, when differentiating into osteoblasts, they express, besides osteocalcin, also flk-1 (VEGF-R2). In addition, 30% of them expressed specific antigens for endothelial cells, including CD54, von-Willebrand (domain 1 and 2), CD31 (PECAM-1) and angiotensin-converting enzyme. Interestingly, we found endotheliocytes forming vessel walls, observing that stem cells synergically differentiate into osteoblasts and endotheliocytes, and that flk-1 exerts a pivotal role in coupling osteoblast and endotheliocyte differentiation. When either SBP-DPSCs or bone chips obtained in vitro were transplanted into immunocompromised rats, they generated a tissue structure with an integral blood supply similar to that of human adult bone; in fact, a large number of HLA-1+ vessels were observed either within the bone or surrounding it in a periosteal layer. This study provides direct evidence to suggest that osteogenesis and angiogenesis mediated by human SBP-DPSCs may be regulated by distinct mechanisms, leading to the organization of adult bone tissue after stem cell transplantation.
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              Three years after transplants in human mandibles, histological and in-line holotomography revealed that stem cells regenerated a compact rather than a spongy bone: biological and clinical implications.

              Mesenchymal stem cells deriving from dental pulp differentiate into osteoblasts capable of producing bone. In previous studies, we extensively demonstrated that, when seeded on collagen I scaffolds, these cells can be conveniently used for the repair of human mandible defects. Here, we assess the stability and quality of the regenerated bone and vessel network 3 years after the grafting intervention, with conventional procedures and in-line holotomography, an advanced phase-imaging method using synchrotron radiation that offers improved sensitivity toward low-absorbing structures. We found that the regenerated tissue from the graft sites was composed of a fully compact bone with a higher matrix density than control human alveolar spongy bone from the same patient. Thus, the regenerated bone, being entirely compact, is completely different from normal alveolar bone. Although the bone regenerated at the graft sites is not of the proper type found in the mandible, it does seem to have a positive clinical impact. In fact, it creates steadier mandibles, may well increase implant stability, and, additionally, may improve resistance to mechanical, physical, chemical, and pharmacological agents.
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                Author and article information

                Journal
                Med Oral Patol Oral Cir Bucal
                Med Oral Patol Oral Cir Bucal
                Medicina Oral S.L.
                Medicina Oral, Patología Oral y Cirugía Bucal
                Medicina Oral S.L.
                1698-4447
                1698-6946
                July 2018
                21 June 2018
                : 23
                : 4
                : e469-e477
                Affiliations
                [1 ]MD, PhD, Professor, Cruces University Hospital, BioCruces Health Research Institute, University of the Basque Country
                [2 ]PharD, PhD, Pharmacist, BioCruces Heath Research Institute
                [3 ]MD, Neuroradiologist, Cruces University Hospital, BioCruces Heath Research Institute
                [4 ]MD, PhD, Associate Professor, University of the Basque Country, BioCruces Health Research Institute
                Author notes
                University of Basque Country Departamento de Estomatología c/ Barrio Sarriena s/n 48940 Leioa Bizkaia , E-mail: arteagoitia@ 123456gmail.com

                Conflict of interest statement: The first author of this manuscript and all co-authors declare no potential conflict of interest related to this study.

                Article
                22466
                10.4317/medoral.22466
                6051678
                29924768
                5f2830a2-e78b-466b-9fe7-5e45f6fe3599
                Copyright: © 2018 Medicina Oral S.L.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 June 2018
                : 15 March 2018
                Categories
                Research
                Oral Surgery

                Surgery
                Surgery

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