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Background and Aims: In the case of mucous membrane pemphigoid with gingival expression (gMMP), the complete healing of the gingiva is generally not achieved despite medical treatment. Therefore, patients' oral comfort is impaired. The dysbiotic periodontal microbiota, generated by a lack of oral hygiene associated with persistent gingival pain, could the immunopathological mechanism to persist. The main objective of this study was to characterize the subgingival microbiota of the gMMP patients, and to highlight a potential link between this microbiological data and the clinical data. Methods: Subgingival biofilm was collected from 15 gMMP patients, medically treated or not, but not receiving periodontal treatment. The usual clinical periodontal parameters were recorded. The biofilm was analyzed by polymerase chain reaction quantitative. The risk factors of severe erosive gingivitis and severe periodontitis were assessed using Chi-square or Fischer's exact test were used. Results: Whatever the medical and periodontal conditions of the patients, the results showed the existence of three main communities of periodontopathic, dysbiotic bacteria. The first including Tannnerella forsythia, Peptostreptococcus micros, Fusobacterium nucleatum, and Campylobacter rectus, was found in 100% of the patients, the second enriched with Treponema denticola in 60% and the third enriched with Porphyromonas gingivalis and Prevotella intermedia in 26%. Furthermore, there was a significant positive link between the duration of gMMP and the severity of erosive gingivitis (p = 0.009), and the loss of deep periodontal tissue (p = 0.04). Conclusion: This pilot study suggests a high periodontal risk in gMMP patients. The pathological processes, autoimmune on the one hand and plaque-induced on the other, may amplify each other. The application of periodontal therapy is therefore necessary in parallel with medical treatment. Nevertheless, further controlled studies are required to validate and complement these preliminary results.
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Mesenchymal stem cell secretome or conditioned medium (MSC-CM) is a combination of biomolecules and growth factors in cell culture growth medium, secreted by mesenchymal stem cells (MSCs), and the starting point of several derived products. MSC-CM and its derivatives could be applied after injuries and could mediate most of the beneficial regenerative effects of MSCs without the possible side effects of using MSCs themselves. However, before the clinical application of these promising biopharmaceuticals, several issues such as manufacturing protocols and quality control must be addressed. This review aims to underline the influence of the procedure for conditioned medium production on the quality of the secretome and its derivatives and highlights the questions considering cell sources and donors, cell expansion, cell passage number and confluency, conditioning period, cell culture medium, microenvironment cues, and secretome-derived product purification. A high degree of variability in MSC secretomes is revealed based on these parameters, confirming the need to standardize and optimize protocols. Understanding how bioprocessing and manufacturing conditions interact to determine the quantity, quality, and profile of MSC-CM is essential to the development of good manufacturing practice (GMP)-compliant procedures suitable for replacing mesenchymal stem cells in regenerative medicine.
Assuntos
Células-Tronco Mesenquimais , Secretoma , Meios de Cultivo Condicionados/farmacologia , Controle de Qualidade , Padrões de ReferênciaRESUMO
Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.
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Stem cells discovery and their potential have led to the emergence of new forms of therapy with the development of bio-engineering cell and tissue methods underlying future medicine. The availability of stem cells and their preservation thus become an issue for everyone's health. Among the different sources of stem cells, those in the dental pulp have the advantage of being pluripotent, they can be cryopreserved and stored for long periods without losing their multiplication and differentiation capacities and finally they are easily accessible. The wisdom or natal teeth extracted for medical reasons are an opportunity for everyone to preserve stem cells for an autologous use. Biobanks authorized and specialized in the preparation and storage of pulp stem cells provide access to autologous regenerative medicine of tomorrow.