Fernando de Sá Silva

Intestinal Microbiota as Modulators of the Immune System and Neuroimmune System: Impact on the Host Health and Homeostasis

Many immune-based intestinal disorders, such as ulcerative colitis and Crohns disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work—gut microbiota, immune system, and their influence in the neuroimmune system.

Toward Personalized Cell Therapies by Using Stem Cells: Seven Relevant Topics for Safety and Success in Stem Cell Therapy

Stem cells, both embryonic and adult, due to the potential for application in tissue regeneration have been the target of interest to the world scientific community. In fact, stem cells can be considered revolutionary in the field of medicine, especially in the treatment of a wide range of human diseases. However, caution is needed in the clinical application of such cells and this is an issue that demands more studies. This paper will discuss some controversial issues of importance for achieving cell therapy safety and success. Particularly, the following aspects of stem cell biology will be presented: methods for stem cells culture, teratogenic or tumorigenic potential, cellular dose, proliferation, senescence, karyotyping, and immunosuppressive activity.

Mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs) induce immune modulatory profile in monocyte-derived dendritic cells.

Background Mesenchymal stem cells have prominent immune modulatory properties, which may have clinical applications; however their major source, bone marrow, is of limited availability. On the other hand, mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs) are readily accessible, but their immune regulatory properties have not been completely investigated. This study was designed, therefore, to evaluate the SHEDs influence on DCs differentiation, maturation, ability to activate T cells and to expand CD4+Foxp3+ T cells. Methodology/Principal Findings The experiments were based in cellular co-culture during differentiation and maturation of monocyte derived-DCs (moDCs), with, or not, presence of SHEDs. After co-culture with SHEDs, (moDCs) presented lower expression of BDCA-1 and CD11c, in comparison to DC cultivated without SHEDs. CD40, CD80, CD83 and CD86 levels were also decreased in mature DCs (mDCs) after co-cultivation with SHEDs. To assess the ability of SHEDs-exposed moDCs to modulate T cell responses, the former were separated from SHEDs, and co-cultured with peripheral blood lymphocytes. After 5 days, the proliferation of CD4+ and CD8+ T cells was evaluated and found to be lower than that induced by moDCs cultivated without SHEDs. In addition, an increase in the proportion of CD4+Foxp3+IL-10+ T cells was observed among cells stimulated by mature moDCs that were previously cultivated with SHEDs. Soluble factors released during co-cultures also showed a reduction in the pro-inflammatory cytokines (IL-2, TNF-α and IFN-γ), and an increase in the anti-inflammatory molecule IL-10. Conclusion/Significance This study shows that SHEDs induce an immune regulatory phenotype in moDCs cells, evidenced by changes in maturation and differentiation rates, inhibition of lymphocyte stimulation and ability to expand CD4+Foxp3+ T cells. Further characterization and validation of this phenomenon could support the use of SHEDs, directly or indirectly for immune modulation in the clinical practice.

Immunoregulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in the Nasal Polyp Microenvironment

Nasal polyposis is a severe, chronic inflammatory condition of the paranasal sinuses and is frequently associated with asthma and aspirin sensitivity. Mesenchymal stem cells exhibit a potent immunosuppressive effect in several inflammatory conditions, and their role in nasal polyposis remains little explored. Hence, we investigated whether bone marrow-derived mesenchymal stem cells could modulate cell phenotype in the nasal polyp milieu. After coculture with mesenchymal stem cells, the frequency of these inflammatory cells was found to decrease. Furthermore, mesenchymal stem cells promoted strong inhibition of CD4+ and CD8+ T cell proliferation, increased the frequency of CD4+CD25+Foxp3 T cells, and changed the global cytokine profile from an inflammatory to an anti-inflammatory response. We believe that mesenchymal stem cells may be a very useful adjunct for investigation of the inflammatory process in nasal polyposis, contributing to better understanding of the inflammatory course of this condition.

Satellite Cells: Regenerative Mechanisms and Applicability in Muscular Dystrophy

The satellite cells are long regarded as heterogeneous cell population, which is intimately linked to the processes of muscular recovery. The heterogeneous cell population may be classified by specific markers. In spite of the significant amount of variation amongst the satellite cell populations, it seems that their activity is tightly bound to the paired box 7 transcription factor expression, which is, therefore, used as a canonical marker for these cells. Muscular dystrophic diseases, such as Duchenne muscular dystrophy, elicit severe tissue injuries leading those patients to display a very specific pattern of muscular recovery abnormalities. There have been works on the application of precursors cells as a therapeutic alternative for Duchenne muscular dystrophy and initial attempts have proven the cells inefficient; however later endeavours have proposed solutions for the experiments improving significantly the results. The presence of a range of satellite cells populations indicates the existence of specific cells with enhanced capability of muscular recovery in afflicted muscles.

Dental pulp stem cells express proteins involved in the local invasiveness of odontogenic myxoma

Little is known about the histogenesis of the odontogenic myxoma (OM). Dental pulp stem cells could be candidate precursors of OM because both OM and the dental pulp share the same embryological origin: the dental papilla. For the purpose of comparing OM and stem cells, this study analyzed the expression of two proteins related to OM invasiveness (MMP-2 and hyaluronic acid) in human immature dental pulp stem cells (hIDPSCs). Three lineages of hIDPSCs from deciduous and permanent teeth were used in this study. Immunofluorescence revealed positive reactions for MMP-2 and hyaluronic acid (HA) in all hIDPSCs. MMP-2 appeared as dots throughout the cytoplasm, whereas HA appeared either as diffuse and irregular dots or as short fibrils throughout the cytoplasm and outside the cell bodies. The gene expression profile of each cell lineage was evaluated using RT-PCR analysis, and HA was expressed more intensively than MMP-2. HA expression was similar among the three hIDPSCs lineages, whereas MMP-2 expression was higher in DL-1 than in the other cell lines. The expression of proteins related to OM invasiveness in hIDPSCs could indicate that OM originates from dental pulp stem cells.

Advances in cellular technology in the hematology field: What have we learned so far?

Despite the advances in the hematology field, blood transfusion-related iatrogenesis is still a major issue to be considered during such procedures due to blood antigenic incompatibility. This places pluripotent stem cells as a possible ally in the production of more suitable blood products. The present review article aims to provide a comprehensive summary of the state-of-the-art concerning the differentiation of both embryonic stem cells and induced pluripotent stem cells to hematopoietic cell lines. Here, we review the most recently published protocols to achieve the production of blood cells for future application in hemotherapy, cancer therapy and basic research.