Improving the Therapeutic Ability of Mesenchymal Stem/Stromal Cells for the Treatment of Conditions Influenced by Immune Cells

Mesenchymal stem/stromal cells (MSCs) have been initially described decades ago as fibroblastic precursors that could be isolated from the bone marrow and establish cultures of fibroblastic cells. These fibroblastic cells were shown tosupport hematopoiesis in vitro, which is a characteristic of stromal cells, and, later, to give rise to mature mesenchymal cells such as bone, cartilage, and fat cells when cultured under appropriate conditions. The proposition that a mesenchymal stem cell exists in postnatal bone marrow and other tissues asblood vessel-associated cells provided further momentum to research on these cells, as well as divergences on how to call them. The impetus of using MSCs to replace cells lost in various types of conditions eventually decreased, as the therapeutic benefits provided by these cells were found to be mostly due to the secretion of paracrine signaling molecules,which can be carried by extracellular vesicles. In the meantime, MSCs were found to modulate the behavior of immunecells by means of secretion of molecules that could, in different scenarios, inhibit the activation of T cells that promote adaptive immune responses. Subsequently, the effects of MSCs on other cells of the immune system were alsodescribed. Today, a number of clinical trials using MSCs to treat conditions influenced by immune cells are under way. While preclinical data indicates that MSCs have important immunomodulatory properties, further studies are still in progress to increase the knowledge on the differences regarding the action of MSCs on immune cells according to their tissue of origin, on how MSCs exert their effects on the different types of immune cells, and on ways to improve the outcome of conditions influenced by immune cells when treated using MSCS.Fil: da Silva Meirelles, Lindolfo. Universidad Luterana; BrasilFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Medeiros Markoski, Melissa. Universidad Federal de Ciencias de la Salud ; BrasilFil: Dallagiovanna, Bruno. Carlos Chagas Institute - Fiocruz; BrasilFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentin

Short-term exercise training improves cardiac function associated to a better antioxidant response and lower type 3 iodothyronine deiodinase activity after myocardial infarction

Aims: We assessed the effects of a short-term exercise training on cardiac function, oxidative stress markers, and type 3 iodothyronine deiodinase (D3) activity in cardiac tissue of spontaneously hypertensive rats (SHR) following experimental myocardial infarction (MI). Methods: Twenty-four SHR (aged 3 months) were allocated to 4 groups: sham+sedentary, sham+trained, MI+sedentary and MI+trained. MI was performed by permanent ligation of the coronary artery. Exercise training (treadmill) started 96 hours after MI and lasted for 4 weeks (~60% maximum effort, 4x/week and 40 min/day). Cardiac function (echocardiography), thioredoxin reductase (TRx), total carbonyl levels, among other oxidative stress markers and D3 activity were measured. A Generalized Estimating Equation was used, followed by Bonferroni’s test (p<0.05). Results: MI resulted in an increase in left ventricular mass (p = 0.002) with decreased cardiac output (~22.0%, p = 0.047) and decreased ejection fraction (~41%, p = 0.008) as well as an increase in the carbonyl levels (p = 0.001) and D3 activity (~33%, p<0.001). Exercise training resulted in a decrease in left ventricular mass, restored cardiac output (~34%, p = 0.048) and ejection fraction (~20%, p = 0.040), increased TRx (~85%, p = 0.007) and reduced carbonyl levels (p<0.001) and D3 activity (p<0.001). Conclusions: Our short-term exercise training helped reverse the effects of MI on cardiac function. These benefits seem to derive from a more efficient antioxidant response and lower D3 activity in cardiac tissue

Maternal ingestion of cocoa causes constriction of fetal ductus arteriosus in rats

Maternal consumption of polyphenol-rich foods has been associated with fetal ductus arteriosus constriction (DAC), but safety of chocolate exposure in fetal life has not been studied. This experimental study tested the hypothesis that maternal cocoa consumption in late pregnancy causes fetal DAC, with possible associated antioxidant effects. Pregnant Wistar rats, at the 21st gestational day, received by orogastric tube cocoa (720 mg/Kg) for 12 h, indomethacin (10 mg/Kg), for 8 h, or only water, before cesaren section. Immediately after withdrawal, every thorax was obtained and tissues were fixed and stained for histological analysis. The ratio of the narrowest part of the pulmonary artery to the fetal ductus inner diameter and increased ductal inner wall thickness characterized ductal constriction. Substances reactive to thiobarbituric acid were quantified. Statistical analysis used ANOVA and Tukey test. Cocoa (n = 33) and indomethacin (n = 7) reduced fetal internal ductus diameter when compared to control (water, n = 25) (p < 0.001) and cocoa alone increased ductus wall thickness (p < 0.001), but no change was noted in enzymes activity. This pharmacological study shows supporting evidences that there is a cause and effect relationship between maternal consumption of cocoa and fetal ductus arteriosus constriction. Habitual widespread use of chocolate during gestation could account for undetected ductus constriction and its potentially severe consequences, such as perinatal pulmonary hypertension, cardiac failure and even death. For this reason, dietary guidance in late pregnancy to avoid high chocolate intake, to prevent fetal ductal constriction, may represent the main translational aspect of this study

Estudo do desenvolvimento in vitro de Mesocestoides corti (Platyhelminthes : Cestoda) : 1. análise do efeito de drogas anti-helmínticas; 2. estabelecimento de linhagens celulares

Mesocestoides corti é um platelminto endoparasita pertencente à classe Cestoda. Devido a sua capacidade de reprodução assexual in vivo, em hospedeiros experimentais, e in vitro, em condições apropriadas de cultura, é considerado um bom modelo para diversos estudos sobre a biologia de cestódeos. O desenvolvimento da fase larval na forma adulta de M. corti foi previamente padronizado in vitro pelo nosso grupo. Assim, este trabalho tem como objetivos principais o estudo, em nível morfológico, das modificações teciduais, que ocorrem durante o desenvolvimento de tetratirídeo a adulto in vitro, e a análise do efeito da exposição destes tecidos e fases a drogas anti-helmínticas de amplo espectro. Visando, futuramente, estudar o efeito de drogas antihelmínticas sobre morfologia e mecanismos celulares, o trabalho também aborda o estabelecimento de culturas celulares primárias a partir de diferentes fases do desenvolvimento in vitro de M. corti. Foi verificado por microscopia confocal que, durante o processo de estrobilização (desenvolvimento da larva na fase adulta) in vitro, houve grande rearranjo da arquitetura corporal principalmente no tegumento, sistema muscular e formação dos órgãos sexuais. Estes tecidos são severamente atingidos pela ação de praziquantel e albendazol. Foi observado que vermes estrobilados foram os mais afetados por ação das drogas. Culturas celulares foram estabelecidas a partir da fase adulta e larval do parasito, cujas células dispõem-se em diferentes subpopulações com tamanhos variando de 2 a 7m, proliferativas e metabolicamente ativas sintetizando matriz extracelular. Parte da matriz extracelular sintetizada foi caracterizada onde foi constatada a presença de carboidratos neutros e carregados, GAGs e proteínas. Este trabalho contribuiu para um melhor entendimento da dinâmica das alterações morfológicas de M. corti, modelo para platelmintos parasitos, e abre a possibilidade de estudos mais detalhados da arquitetura corporal frente à exposição a drogas anti-helmínticas e estudos focalizados, do efeito destas drogas em nível celular, através do estabelecimento das culturas celulares.Mesocestoides corti is an endoparasitic flatworm belonging to the Cestoda class. Due to the in vivo asexual reproduction capability, in experimental hosts, and in vitro, in appropriated culture conditions, M. corti is considered a good model to many studies of the cestode biology. The M. corti in vitro development of larva in adult worm was standardized by our group. Thus, this work has as main objectives the morphologic study of the tissue changes that occur during the tetrathyridium to adult in vitro development and the exposition of these tissues and life phases to broad-spectrum antihelminthic drugs. With the future aim of study antihelminthic drug effect on cell morphology and physiology, the work also shows the establishment of primary cultures of cells from different in vitro developmental stages of M. corti. Using laser-scanning confocal microscopy, we demonstrated that there were body architecture rearrangements during the in vitro development occurring strongly in tegument, muscle system and sexual organs. These tissues are severely damaged by antihelminthic drugs as praziquantel and albendazole. During development, the adult stage is the most damaged by the drug action. Cell cultures were established from the parasite adult and larval phases, which were distributed in different subpopulations having diameters varying between 2 and 7m. Cultured cells are proliferative and metabolic actives, with synthesis of extracellular matrix. The extracellular matrix composition was preliminarily determined and it was shown that neutral and charged carbohydrates, GAGs and proteins were present. Thus, this work contributed to a better comprehension about the morphological rearrangement dynamics of M. corti, a flatworm model, and makes possible a more detailed study of the body architecture on antihelminthic drug exposition. As well as, this work will allow focused studies of the drug effect at cellular level favoured by cell culture establishment from a parasite

Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice

Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals

Análise de linhagens celulares de Mesocestoides corti (Platyhelminthes: Cestoda) por microscopia eletrônica de varredura e transmissão

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Análise de linhagens celulares de Mesocestoides corti (Platyhelminthes: Cestoda) por microscopia eletrônica de varredura e transmissão

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Estabelecimento de linhagem celular de Mesocestoides corti (Platyhelmintes, Cestoda) a partir de indivíduos em processo de estrobilização

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