Navegando por Palavras-chave "Mesenchymal Stem Cell"

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    Efeitos do exercício resistido e do transplante de células tronco mesenquimais em camundongos transgênicos para a doença de Alzheimer
    (Universidade Federal de São Paulo (UNIFESP), 2019-10-31) Hashiguchi, Debora [UNIFESP]; Monteiro, Beatriz De Oliveira [UNIFESP]; http://lattes.cnpq.br/0245964878412260; http://lattes.cnpq.br/0793074422554642; Universidade Federal de São Paulo (UNIFESP)
    Objective: In the present study, we analyzed the effects of the resistance exercise (RE) program or the bone-marrow mesenchymal stem cells (MSC) intra-hippocampal transplantation in the locomotor behavior, as well as amyloid load and inflammatory responses, in the hippocampus of mice model of Alzheimer’s disease (AD). Methods: Double transgenic APP/PS1, 6-7 month-old, male mice were used as Alzheimer's disease model, and the respective wild type (WT) littermates as controls. The animals were divided into six groups: WT; WT submitted to RE (WT+RE); WT submitted to MSC transplantation (WT+MSC); APP/PS1 group; APP/PS1 submitted to exercise program (APP/PS1+RE); and APP/PS1 submitted to transplantation (APP/PS1+MSC). The RE groups (WT+RE and APP/PS1+RE) performed 5 weeks of RE program. To the MSC transplantation, the MSC were extracted from C57BL/6- eGFP+ transgenic mice at 4/6 weeks old. The cells were maintained in culture until 7- 10th passage, when they were transplanted in the MSC groups (WT+MSC and APP/PS1+MSC). At the age of 7-8 months old, with the end of the RE program or 5 weeks after the transplantation, the animals performed the Open Filed Task and then were euthanized for the processing of the brain tissues by immunohisochemistry for 6E10 and Iba-1 markers and the hippocampus was analyzed by stereology. Fresh hippocampus samples were collected from the decapitated animals to quantify the expression of Aβ1-42 peptide by ELISA essay and IL-1α, IL-4, IL-6, IL-10 by MilliplexMAP analysis. Results: APP/PS1 mice presented hyper locomotion, Aβ plaques formation and higher levels of IL-1α, IL-6, IL-4 cytokines. APP/PS1+RE group maintained the locomotion behavior to WT group levels; presented decreased Aβ plaques; increased microglia recruitment compared to WT+RE group; and reduced levels of pro-inflammatory cytokines, near WT group. After 6 weeks of treatment, APP/PS1+MSC group presented increased microglia recruitment, but there are no treatment effect in locomotion, Aβ load or cytokine levels. Conclusions: Our study indicates that RE shows beneficial effects on the behavior, amyloid burden and inflammation presented in AD and therefore has therapeutic potential for the improvement of AD neuropathology. After 6 weeks, the MSC transplantation presented no differences other than microglial recruitment. According to our results RE was shown to be a more effective treatment for AD-related behavioral, amyloid- xi loading and inflammatory changes compared to the intra-hipocampal MSC transplantation.
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    Influência Do Meio De Cultivo Condicionado De Células-Tronco Mesenquimais No Desenvolvimento Embrionário Murino Até O Estágio De Blastocisto
    (Universidade Federal de São Paulo (UNIFESP), 2018-05-22) Silveira, Larissa Berioni Rodrigues Da [UNIFESP]; Turco, Edson Guimaraes Lo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objective: Evaluate The Influence Of The Conditioned Culture Medium From Endometrial Mesenchymal Stem Cells In The Embryonic Cell Culture Method: 544 Murine Embryos Were Divided In 3 Groups: Control (Regular Embryonic Culture Medium); Supplemented (Embryonic Culture Medium Supplemented With Conditioned Imdm Medium After Endometrial Mesenchymal Stem Cell Culture); And Negative Control (Regular Embryonic Culture Medium Supplemented With Imdm Medium). Embryonic Development Was Evaluated In Each Group And Culture Media Were Collected For Metabolomic Analysis By Mass Spectrometry. The Data Were Normalized By Z-Score And Submitted To The Pca And Pls-Da Tests Using The Software Metaboanalyst 3.0, To Identify The Molecular Markers. Results: In The Comparison Between The Three Groups, The Control Group Presented A Higher Blastocyst Rate On The Sixth Day Of Embryo Culture In Relation To The Supplemented And Negative Control Groups (0,3 ± 0,160; 0,01±0,01; 0,00±0,00, Respectively) , While The Rate Of Degenerate Was High
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    Papel do receptor aril-hidrocarboneto na atividade imunomoduladora das células-tronco mesenquimais utilizando um modelo de lesão renal aguda
    (Universidade Federal de São Paulo (UNIFESP), 2019-04-25) Evangelista, Laura Sibele Martins [UNIFESP]; Almeida, Danilo Candido De [UNIFESP]; http://lattes.cnpq.br/8395461764493766; http://lattes.cnpq.br/5737372141735502; Universidade Federal de São Paulo (UNIFESP)
    Acute kidney injury (AKI) affects millions of people worldwide with elevated mortality rate. AKI is characterized by an acute tissue inflammation with influx of inflammatory cells. The aryl-hydrocarbon receptor (AhR) is a transcription factor present in several cells and in inflammatory infiltrating cells being involved mainly in the regulation of various biological processes including the immune response. In this context, mesenchymal stem cells (MSCs) have a great immunotherapeutic potential, which can be regulated by specific receptors such as AhR. Thus, the precise mechanism associated to AhR activation in MSCs and its therapeutic role in AKI remains poorly elucidated. Therefore, in this study, we evaluated the activation of MSCs via AhR and functionally tested its therapy in an experimental model of cisplatin-induced AKI (15mg/kg, CEUA: 9656080916). Mouse adipose tissue-derived MSCs were expanded in cultures and activated with both kynurenine (KY, 50μM) or tetrachlorodibenzo-p-dioxin (TCDD, 0.2μM) agonists, which are natural and synthetic AhR inducers, respectively. At day 4 after cytotoxic injury, serum and renal tissues were collected to performing several analyzes (colorimetric, RT-PCR, flow cytometry, immunohistochemical and histopathological assays). First, we observed that MSCs were perfectly activated by AhR and expressed, in a dose-dependent manner, high levels of AhR responsive genes and its accessory molecules (CYP1b1, AhR and ARNT). In addition, these stimulated MSCs presented higher kinetics in culture (>Ki-67). Then, it was observed after both treatments with MSCs (unstimulated and KY-stimulated) similar protection in AKI-affected animals such as: lower weight loss, low creatinine and urea levels, preserved tubular renal architecture, reduced tissue apoptosis (caspase- 3) and diminished inflammation (IL-6, CCL2 and TNF-α). Moreover, we specifically analyzed in situ renal monocytes/macrophages (CD68 cells) and found lower cumulative frequency of these cells in mice treated with unstimulated MSCs. Renal macrophages (F4/80+/CD11b+) from group that received infusion of unstimulated MSCs also had an up-regulation of its immunoregulatory profile with decreased expression of M1 inflammatory markers (CCL2 and STAT3) and increased expression of M2 molecules (CD206, FIZZ1 and CX3CR1). Finally, we investigated the expression of genes associated with renal tissue metabolism and it was verified in kidneys of animals injected with unstimulated MSCs a reduced glycolytic profile (low HK2 and PK), whereas that kidneys of animals treated with KY-stimulated MSCs presented a β-oxidative pattern (high CPTA2 and ACOX1). In summary, we have documented that MSCs can be stimulated by KY via AhR and this licensing affected partially its immunoregulatory activities on renal macrophages in a model of cisplatin-induced AKI without impairing renoprotection. We believe that our findings could contribute with some insights concerning the mechanisms associated with MSCs activation and its application in several inflammatory diseases facilitating thus, its better therapeutic translation for clinical practice.