Background: One of the greatest challenges for medicine is to find a safe and effective treatment for immune-related diseases. However, due to the low efficacy of the treatment available and the occurrence of serious adverse effects, many groups are currently searching for alternatives to the traditional therapy. In this regard, the use of human mesenchymal stem cells (hMSCs) represents a great promise for the treatment of a variety of immune-related diseases due to their potent immunomodulatory properties. The main objective of this study is, therefore, to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of the administration of hMSCs for the treatment of immune-related diseases was evaluated.Methods: The article search was conducted in PubMed/MEDLINE, Scopus and Web of Science databases. Original research articles assessing the therapeutic potential of hMSCs administration for the in vivo treatment immune-related diseases, published from 1984 to December 2017, were selected and evaluated.Results: A total of 132 manuscripts formed the basis of this systematic review. Most of the studies analyzed reported positive results after hMSCs administration. Clinical effects commonly observed include an increase in the survival rates and a reduction in the severity and incidence of the immune-related diseases studied. In addition, hMSCs administration resulted in an inhibition in the proliferation and activation of CD19+ B cells, CD4+ Th1 and Th17 cells, CD8+ T cells, NK cells, macrophages, monocytes, and neutrophils. The clonal expansion of both Bregs and Tregs cells, however, was stimulated. Administration of hMSCs also resulted in a reduction in the levels of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-1, IL-2, IL-12, and IL-17 and in an increase in the levels of immunoregulatory cytokines such as IL-4, IL-10, and IL-13.Conclusions: The results obtained in this study open new avenues for the treatment of immune-related diseases through the administration of hMSCs and emphasize the importance of the conduction of further studies in this area.

Dental pulp represents a promising and easily accessible source of mesenchymal stem cells for clinical applications. Many studies have investigated the use of human dental pulp stem cells and stem cells isolated from the dental pulp of human exfoliated deciduous teeth for bone tissue engineering in vivo. However, the type of scaffold used to support the proliferation and differentiation of dental stem cells, the animal model, the type of bone defect created, and the methods for evaluation of results were extremely heterogeneous among these studies conducted. With this issue in mind, the main objective of this study is to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of human dental pulp stem cells and stem cells from human exfoliated deciduous teeth (SHED) for bone regeneration was evaluated. The article search was conducted in PubMed/MEDLINE and Web of Science databases. Original research articles assessing potential of human dental pulp stem cells and SHED for in vivo bone tissue engineering, published from 1984 to November 2017, were selected and evaluated in this review according to the following eligibility criteria: published in English, assessing dental stem cells of human origin and evaluating in vivo bone tissue formation in animal models or in humans. From the initial 1576 potentially relevant articles identified, 128 were excluded due to the fact that they were duplicates and 1392 were considered ineligible as they did not meet the inclusion criteria. As a result, 56 articles remained and were fully analyzed in this systematic review. The results obtained in this systematic review open new avenues to perform bone tissue engineering for patients with bone defects and emphasize the importance of using human dental pulp stem cells and SHED to repair actual bone defects in an appropriate animal model.

Background A new trend in the treatment for alveolar clefts in patients with cleft lip and palate involves the use of bone tissue engineering strategies to reduce or eliminate the morbidity associated with autologous bone grafting. The use of mesenchymal stem cells—autologous cells obtained from tissues such as bone marrow and fat—combined with various biomaterials has been proposed as a viable option for use in cleft patients. However, invasive procedures are necessary to obtain the mesenchymal stem cells from these two sources. To eliminate donor site morbidity, noninvasive stem cell sources such as the umbilical cord, orbicularis oris muscle, and deciduous dental pulp have been studied for use in alveolar cleft bone tissue engineering. In this study, we evaluate the osteogenic potential of these various stem cell types. Methods Ten cellular strains obtained from each different source (umbilical cord, orbicularis oris muscle, or deciduous dental pulp) were induced to osteogenic differentiation in vitro, and the bone matrix deposition of each primary culture was quantified. To evaluate whether greater osteogenic potential of the established mesenchymal stem cell strains was associated with an increase in the expression profile of neural crest genes, real-time qPCR was performed on the following genes: SRY-box 9, SRY-box 10, nerve growth factor receptor, transcription factor AP-2 alpha, and paired box 3. Results The mesenchymal stem cells obtained from deciduous dental pulp and orbicularis oris muscle demonstrated increased osteogenic potential with significantly more extracellular bone matrix deposition when compared to primary cultures obtained from the umbilical cord after twenty-one days in culture (p = 0.007 and p = 0.005, respectively). The paired box 3 gene was more highly expressed in the MSCs obtained from deciduous dental pulp and orbicularis oris muscle than in those obtained from the umbilical cord. Conclusion These results suggest that deciduous dental pulp and orbicularis oris muscle stem cells demonstrate superior osteogenic differentiation potential relative to umbilical cord-derived stem cells and that this increased potential is related to their neural crest origins. Based on these observations, and the distinct translational advantage of incorporating stem cells from noninvasive tissue sources into tissue engineering protocols, greater study of these specific cell lines in the setting of alveolar cleft repair is indicated.

Mesenchymal stem cells (MSCs) have been studied as a promising type of stem cell for use in cell therapies because of their ability to regulate the immune response. Although they are classically isolated from the bone marrow, many studies have sought to isolate MSCs from noninvasive sources. The objective of this study was to evaluate how MSCs isolated from the dental pulp of human exfoliated deciduous teeth (SHED) and fragments of the orbicularis oris muscle (OOMDSCs) behave when treated with an inflammatory IFN-γ stimulus, specifically regarding their proliferative, osteogenic, and immunomodulatory potentials. The results demonstrated that the proliferation of SHED and OOMDSCs was inhibited by the addition of IFN-γ to their culture medium and that treatment with IFN-γ at higher concentrations resulted in a greater inhibition of the proliferation of these cells than treatment with IFN-γ at lower concentrations. SHED and OOMDSCs maintained their osteogenic differentiation potential after stimulation with IFN-γ. Additionally, SHED and OOMDSCs have been shown to have low immunogenicity because they lack expression of HLA-DR and costimulatory molecules such as CD40, CD80, and CD86 before and after IFN-γ treatment. Last, SHED and OOMDSCs expressed the immunoregulatory molecule HLA-G, and the expression of this antigen increased after IFN-γ treatment. In particular, an increase in intracellular HLA-G expression was observed. The results obtained suggest that SHED and OOMDSCs lack immunogenicity and have immunomodulatory properties that are enhanced when they undergo inflammatory stimulation with IFN-γ, which opens new perspectives for the therapeutic use of these cells.