Navegando por Palavras-chave "Mesenchymal stromal cells"
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- ItemAcesso aberto (Open Access)Efeito da suplementação com ácidos graxos ômega 3 (ω-3) nas propriedades das células estromais mesenquimais da medula óssea(Universidade Federal de São Paulo (UNIFESP), 2018-12-20) Oliveira, Andreia Silva de [UNIFESP]; Borges, Fernanda Teixeira [UNIFESP]; Schor, Nestor [UNIFESP]; http://lattes.cnpq.br/8276708741672261; http://lattes.cnpq.br/4206613998602417; http://lattes.cnpq.br/4123390663752858; Universidade Federal de São Paulo (UNIFESP)Mesenchymal stromal cells (MSCs) are characterized by the ability to differentiate into mesoderm cells, multiplication to maintain their undifferentiated state and expression of surface markers such as CD90 and CD73, but not CD45, in addition to others. They have ability to target the injured site and present antiinflammatories, antioxidants and immunosuppressants effects. Donor characteristics may influence the characteristics and / or effects of MSCs. This study aimed to perform dietary supplementation with omega3 polyunsaturated fatty acids in the characteristics of mesenchymal stromal cells. Wistar rats were supplemented for 28 days with eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) (2mg/kg body weight), as MSCs were harvested, cultured and analyzed in the 4th passage (MSCs3) and compared with animal cells not supplemented (MSCs). The capacity of selfrenewal, adipogenic and osteogenic differentiation, response to hypoxia and repairing effect in a unilateral ureteral obstruction (UUO) model were analyzed. Differences in morphology and in the differentiation capacity between MSCs and MSCs3 was not observed. The latter has small capacity for selfrenewal, but both showed the same apoptotic rates under hypoxic conditions. In severe chronic diseases induced by UUO, we observed that as MSCs3 aggravated an infiltration of immune cells in relation to obstructed kidneys. In the transplanted kidneys with MSCs3, there was greater expression of superoxide dismutase1, IL10, and less IL6 production. There was no significant fibrosis in the obstructed kidneys, but there were increased levels of TGFβ1 in the UUO group. It decreased in those transplanted with MSCs3, suggesting a longterm antifibrotic effect as observed in MSCs. Our results suggest that supplementation of omega3 donors may interfere with the characteristics and effects of MSCs and supplementation should be taken into account when using these cells for therapy.
- ItemAcesso aberto (Open Access)Imunomodulação promovida pelo transplante de células tronco mesenquimais derivadas de medula óssea em lesões no sistema nervoso central(Universidade Federal de São Paulo (UNIFESP), 2011-02-22) Galindo, Layla Testa [UNIFESP]; Porcionatto, Marimélia Aparecida [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Central nervous system (CNS) injury breakes the impermeability of the blood brain barrier, this allows the invasion of immune cells and activation of glial cells, mainly microglia and astrocytes. This process triggers the secretion of inflammatory mediators by these cells. Cytokines are the main molecules in neuroinflammatory response and are critical for its regulation, exerting a variety of actions in the CNS. Furthermore, mesenchymal stem cells (MSC) which have proliferative potential and are able to originate different and specialized cell lineages, also secrete these molecules, characterizing its immunomodulatory function. MSC, particularly those derived from bone marrow, promote tissue repair by secreting factors that enhance tissue regeneration stimulating proliferation, migration and differentiation of endogenous stem-like progenitors found in most tissues, decreasing inflammatory and immune reactions and apoptosis. The ability of such cells to alter tissue microenvironment through its trophic influence may contribute more significantly than their capacity for transdifferentiation in effecting tissue repair.Our hypothesis is that MSC secreted cytokines could take part in the attraction of endogenous neural stem cells (NSC) to an injury site in the CNS, providing a favorable microenvironment for these cells. Our aim was to study the effects of factors secreted by MSC on NSC in vitro and to analyse the MSC cytokines expression in vivo in a model of CNS traumatic injury. We first evaluated the effects of MSC secreted factors on apoptosis, proliferation and differentiation of adult NSC derived from the subventricular zone and cultured as neurospheres. Neurospheres were cultured in MSC conditioned medium (MSC-CM), which was obtained from bone marrow-derived MSC cultures. Besides a traumatic injury was performed at the primary motor cortex of mice and MSCs were injected at the injury site. Our results show that MSC secreted factors do not induce or prevent NSC apoptosis, increase NSC proliferation and induce bigger expression of GFAP gene in vitro, this could indicate a tendency of differentiation to astrocytes. In vivo experiments show that MSC injection at an acute model of injury diminishes pro-inflamatory cytokines in the injured tissue, suggesting that MSC secreted factors may modulate the inflammation at the injury site, which may be interest to the development favorable microenvironment for endogenous NSC and consequently repair of the injured tissue.
- ItemSomente MetadadadosMesenchymal stromal cells modulate gut inflammation in experimental colitis(Springer Basel Ag, 2018) de Aguiar, Cristhiane Favero; Castoldi, Angela; Andrade-Oliveira, Vinicius; Ignacio, Aline; da Cunha, Flavia Franco [UNIFESP]; Ferreira Felizardo, Raphael Jose [UNIFESP]; Bassi, Enio Jose; Saraiva Camara, Niels Olsen [UNIFESP]; de Almeida, Danilo Candido [UNIFESP]Inflammatory bowel diseases (IBDs) affect millions of people worldwide and their frequencies in developed countries have increased since the twentieth century. In this context, there is an intensive search for therapies that modulate inflammation and provide tissue regeneration in IBDs. Recently, the immunomodulatory activity of adipose tissue-derived mesenchymal stromal cells (ADMSCs) has been demonstrated to play an important role on several immune cells in different conditions of inflammatory and autoimmune diseases. In this study, we explored the immunomodulatory potential of ADMSC in a classical model of DSS-induced colitis. First, we found that treatment of mice with ADMSC ameliorated the severity of DSS-induced colitis, reducing colitis pathological score and preventing colon shortening. Moreover, a prominent reduction of pro-inflammatory cytokines levels (i.e., IFN-gamma, TNF-alpha, IL-6 and MCP-1) was observed in the colon of animals treated with ADMSC. We also observed a significant reduction in the frequencies of macrophages (F4/80(+)CD11b(+)) and dendritic cells (CD11c(+)CD103(+)) in the intestinal lamina propria of ADMSC-treated mice. Finally, we detected the up-regulation of immunoregulatory-associated molecules in intestine of mice treated with ADMSCs (i.e., elevated arginase-1 and IL-10). Thus, this present study demonstrated that ADMSC modulates the overall gut inflammation (cell activation and recruitment) in experimental colitis, providing support to the further development of new strategies in the treatment of intestinal diseases.
- ItemAcesso aberto (Open Access)A reduction in CD90 (THY-1) expression results in increased differentiation of mesenchymal stromal cells(Biomed Central Ltd, 2016) Moraes, Daniela A.; Sibov, Tatiana T. [UNIFESP]; Pavon, Lorena F. [UNIFESP]; Alvim, Paula Q.; Bonadio, Raphael S.; Da Silva, Jaqueline R.; Pic-Taylor, Aline; Toledo, Orlando A.; Marti, Luciana C.; Azevedo, Ricardo B.; Oliveira, Daniela M.Background: Mesenchymal stromal cells (MSCs) are multipotent progenitor cells used in several cell therapies. MSCs are characterized by the expression of CD73, CD90, and CD105 cell markers, and the absence of CD34, CD45, CD11a, CD19, and HLA-DR cell markers. CD90 is a glycoprotein present in the MSC membranes and also in adult cells and cancer stem cells. The role of CD90 in MSCs remains unknown. Here, we sought to analyse the role that CD90 plays in the characteristic properties of in vitro expanded human MSCs. Methods: We investigated the function of CD90 with regard to morphology, proliferation rate, suppression of T-cell proliferation, and osteogenic/adipogenic differentiation of MSCs by reducing the expression of this marker using CD90-target small hairpin RNA lentiviral vectors. Results: The present study shows that a reduction in CD90 expression enhances the osteogenic and adipogenic differentiation of MSCs in vitro and, unexpectedly, causes a decrease in CD44 and CD166 expression. Conclusion: Our study suggests that CD90 controls the differentiation of MSCs by acting as an obstacle in the pathway of differentiation commitment. This may be overcome in the presence of the correct differentiation stimuli, supporting the idea that CD90 level manipulation may lead to more efficient differentiation rates in vitro.
- ItemAcesso aberto (Open Access)Role of aryl hydrocarbon receptor in mesenchymal stromal cell activation: A minireview(Baishideng Publishing Group Inc, 2017) de Almeida, Danilo Candido [UNIFESP]; Martins Evangelista, Laura Sibele [UNIFESP]; Saraiva Camara, Niels Olsen [UNIFESP]Mesenchymal stromal cells (MSCs) possess great therapeutic advantages due to their ability to produce a diverse array of trophic/growth factors related to cytoprotection and immunoregulation. MSC activation via specific receptors is a crucial event for these cells to exert their immunosuppressive response. The aryl-hydrocarbon receptor (AhR) is a sensitive molecule for external signals and it is expressed in MSCs and, upon positive activation, may potentially regulate the MSC-associated immunomodulatory function. Consequently, signalling pathways linked to AhR activation can elucidate some of the molecular cascades involved in MSC-mediated immunosuppression. In this minireview, we have noted some important findings concerning MSC regulation via AhR, highlighting that its activation is associated with improvement in migration and immunoregulation, as well as an increase in pro-regenerative potential. Thus, AhR-mediated MSC activation can contribute to new perspectives on MSC-based therapies, particularly those directed at immune-associated disorders.