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Project description:We provided an mRNA-seq analyses of mouse bone marrow revealing B cell development arrest in the bone marrow after MI, which was restored by treatment of empagliflozin (EMPA).
2022-10-10 | GSE193425 | GEO
Project description:We provided a single cell mRNA-seq analyses of mouse bone marrow revealing B cell development arrest in the bone marrow after MI, which was restored by treatment of empagliflozin (EMPA).
2022-10-10 | GSE193316 | GEO
Project description:Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.
| S-EPMC4913323 | biostudies-literature
Project description:This study aimed to investigate whether exosomes secreted by mouse GATA-4-expressing bone marrow mesenchymal stem cells (BMSCs) could induce BMSC differentiation into myocyte precursors, decrease cardiomyocyte apoptosis, and improve cardiac function following myocardial infarction (MI). BMSCs were transduced with a lentivirus carrying a doxycycline (DOX)-inducible GATA-4 or control lentivirus, and secreted exosomes from these BMSCs were collected and co-cultured with BMSCs or cardiomyocytes under hypoxic and serum free conditions. Furthermore, exosomes were injected into mice 48 h after MI. Cardiac function was evaluated by echocardiography at 48, 72, and 96 h after exosome treatment. Quantitative PCR showed that co-culture of BMSCs with GATA-4-BMSC exosomes increased cardiomyocyte-related marker expression. Co-culture of GATA-4-BMSC exosomes with cardiomyocytes in anoxic conditions decreased apoptosis as detected by flow cytometry. Injection of GATA-4-BMSC exosomes in mice 48 h after MI increased cardiac function over the next 96 h; increased cardiac blood vessel density and number of c-kit-positive cells and decreased apoptotic cardiomyocyte cells were also observed. Differential expression of candidate differentiation- and apoptosis-related miRNAs and proteins that may mediate these effects was also identified. Exosomes isolated from GATA-4-expressing BMSCs induce differentiation of BMSCs into cardiomyocyte-like cells, decrease anoxia-induced cardiomyocyte apoptosis, and improve myocardial function after infarction.
| S-EPMC5998064 | biostudies-literature
Project description:Stem cell transplantation is emerging as a potential therapy to treat heart diseases. Promising results from early animal studies led to an explosion of small, non-controlled clinical trials that created even further excitement by showing that stem cell transplantation improved left ventricular systolic function and enhanced remodelling. However, the specific mechanisms by which these cells improve heart function remain largely unknown. A large variety of cell types have been considered to possess the regenerative ability needed to repair the damaged heart. One of the most studied cell types is the bone marrow-derived mononuclear cells and these form the focus of this review. This review article aims to provide an overview of their use in the setting of acute myocardial infarction, the challenges it faces and the future of stem cell therapy in heart disease.
| S-EPMC3340546 | biostudies-literature
Project description:Treatment of myocardial infarction (MI) with bone marrow cells (BMCs) improves post-MI cardiac function in rodents. However, clinical trials of BMC therapy have been less effective. While most rodent experiments use young healthy donors, patients undergoing autologous cell therapy are older and post-MI. We previously demonstrated that BMCs from aged and post-MI donor mice are therapeutically impaired, and that donor MI induces inflammatory changes in BMC composition including reduced levels of B lymphocytes. Here, we hypothesized that B cell alterations in bone marrow account for the reduced therapeutic potential of post-MI and aged donor BMCs. Injection of BMCs from increasingly aged donor mice resulted in progressively poorer cardiac function and larger infarct size. Flow cytometry revealed fewer B cells in aged donor bone marrow. Therapeutic efficacy of young healthy donor BMCs was reduced by depletion of B cells. Implantation of intact or lysed B cells improved cardiac function, whereas intact or lysed T cells provided only minor benefit. We conclude that B cells play an important paracrine role in effective BMC therapy for MI. Reduction of bone marrow B cells because of age or MI may partially explain why clinical autologous cell therapy has not matched the success of rodent experiments.
| S-EPMC6036225 | biostudies-literature
Project description:Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking H2O2- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer. In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice. This study establishes a cardioprotective role of eosinophils in post-MI hearts.
| S-EPMC7745020 | biostudies-literature
Project description:Hyaluronan (HA) has been shown to play an important role during early heart development and promote angiogenesis under various physiological and pathological conditions. In recent years, stem cell therapy, which may reduce cardiomyocyte apoptosis, increase neovascularization, and prevent cardiac fibrosis, has emerged as a promising approach to treat myocardial infarction (MI). However, effective delivery of stem cells for cardiac therapy remains a major challenge. In this study, we tested whether transplanting a combination of HA and allogeneic bone marrow mononuclear cells (MNCs) promotes cell therapy efficacy and thus improves cardiac performance after MI in rats. We showed that HA provided a favorable microenvironment for cell adhesion, proliferation, and vascular differentiation in MNC culture. Following MI in rats, compared with the injection of HA alone or MNC alone, injection of both HA and MNCs significantly reduced inflammatory cell infiltration, cardiomyocyte apoptosis, and infarct size and also improved cell retention, angiogenesis, and arteriogenesis, and thus the overall cardiac performance. Ultimately, HA/MNC treatment improved vasculature engraftment of transplanted cells in the infarcted region. Together, our results indicate that combining the biocompatible material HA with bone marrow stem cells exerts a therapeutic effect on heart repair and may further provide potential treatment for ischemic diseases.
| S-EPMC3589169 | biostudies-literature
Project description:Ventricular remodeling following myocardial infarction (MI) is a major cause of heart failure, a condition prevalent in older individuals. Following MI, immune cells are mobilized to the myocardium from peripheral lymphoid organs and play an active role in orchestrating repair. While the effect of aging on mouse bone marrow (BM) has been studied, less is known about how aging affects human BM cells and their ability to regulate repair processes. In this study, we investigate the effect aging has on human BM cell responses post-MI using a humanized chimeric mouse model. BM samples were collected from middle aged (mean age 56.4 ± 0.97) and old (mean age 72.7 ± 0.59) patients undergoing cardiac surgery, CD34+/- cells were isolated, and NOD-scid-IL2rγnull (NSG) mice were reconstituted. Three months following reconstitution, the animals were examined at baseline or subjected to coronary artery ligation (MI). Younger patient cells exhibited greater repopulation capacity in the BM, blood, and spleen as well as greater lymphoid cell production. Following MI, CD34+ cell age impacted donor and host cellular responses. Mice reconstituted with younger CD34+ cells exhibited greater human CD45+ recruitment to the heart compared to mice reconstituted with old cells. Increased cellular responses were primarily driven by T-cell recruitment, and these changes corresponded with greater human IFNy levels and reduced mouse IL-1β in the heart. Age-dependent changes in BM function led to significantly lower survival, increased infarct expansion, impaired host cell responses, and reduced function by 4w post-MI. In contrast, younger CD34+ cells helped to limit remodeling and preserve function post-MI.
| S-EPMC8590094 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-03-31 | GSE196867 | GEO