Trials and tribulations of cell therapy for heart failure: an update on ongoing trials.

Heart failure (HF) remains a leading cause of mortality, responsible for 13% of all deaths worldwide. The prognosis for patients with HF is poor, with only a 50% survival rate within 5 years. A major challenge of ischaemia-driven HF is the loss of cardiomyocytes, compounded by the minimal regenerative capacity of the adult heart.

Multidisciplinary Management Strategies for Long COVID: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations.

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction.

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) driven by lipotoxicity is incompletely understood. Given the urgent need for animal models that accurately mimic cardio-metabolic HFpEF, a hyperlipidemia-induced murine model was developed by reverse engineering phenotypes seen in HFpEF patients. This model aimed to investigate HFpEF, focusing on the interplay between lipotoxicity and metabolic syndrome.

Rises in Hematocrit Are Associated With an Increased Risk of Major Adverse Cardiovascular Events in Men Starting Testosterone Therapy: A Retrospective Cohort Claims Database Analysis.

Purpose: Elevated hematocrit (Hct) can result in increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy (TTh). However, the impact of the magnitude of the change in Hct from baseline after starting TTh has never been assessed.

Materials And Methods: To assess whether an increase in Hct after initiating TTh is associated with an increased risk of MACE within 3 and 24 months of initiating TTh, we queried the TriNetX Research network database for men over the age of 18 with Hct values obtained within 6 months before starting TTh, and who had follow-up Hct measurements within 3 and 24 months after beginning TTh from 2010 to 2021.

Mesenchymal STRO-1/STRO-3 precursor cells for the treatment of chronic heart failure with reduced ejection fraction.

The heart is susceptible to proinflammatory and profibrotic responses after myocardial injury, leading to further worsening of cardiac dysfunction. Important developments in the management of heart failure with reduced ejection fraction have reduced morbidity and mortality; however, these therapies focus on optimizing cardiac function through hemodynamic and neurohormonal pathways and not by repairing the underlying cardiac injury. The potential of cell-based therapy to reverse cardiac injury has received substantial attention.

Statistical modeling of extracellular vesicle cargo to predict clinical trial outcomes for hypoplastic left heart syndrome.

Cardiac-derived c-kit+ progenitor cells (CPCs) are under investigation in the CHILD phase I clinical trial (NCT03406884) for the treatment of hypoplastic left heart syndrome (HLHS). The therapeutic efficacy of CPCs can be attributed to the release of extracellular vesicles (EVs). To understand sources of cell therapy variability we took a machine learning approach: combining bulk CPC-derived EV (CPC-EV) RNA sequencing and cardiac-relevant experiments to build a predictive model.

Stem cell therapy for acute myocardial infarction: Mesenchymal Stem Cells and induced Pluripotent Stem Cells.

Introduction: Acute myocardial infarction (AMI) remains a leading cause of death in the United States. The limited capacity of cardiomyocytes to regenerate and the restricted contractility of scar tissue after AMI are not addressed by current pharmacologic interventions. Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach due to their low antigenicity, ease of harvesting, and efficacy and safety in preclinical and clinical studies, despite their low survival and engraftment rates.

The impact of cell-based therapy on female sexual dysfunction: a systematic review and meta-analysis.

Introduction: Female sexual dysfunction (FSD) is a complex issue affecting women of all ages; it involves several overlapping body systems and profoundly affects quality of life. The use of cell-based therapy, such as mesenchymal stem cells, has recently been investigated as a potential treatment for FSD.

Objectives: This systematic review and meta-analysis aim to assess FSD outcomes following cell-based therapy.

HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs.

People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIV) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.

Cell-based therapy to boost right ventricular function and cardiovascular performance in hypoplastic left heart syndrome: Current approaches and future directions.

Congenital heart disease remains one of the most frequently diagnosed congenital diseases of the newborn, with hypoplastic left heart syndrome (HLHS) being considered one of the most severe. This univentricular defect was uniformly fatal until the introduction, 40 years ago, of a complex surgical palliation consisting of multiple staged procedures spanning the first 4 years of the child's life. While survival has improved substantially, particularly in experienced centers, ventricular failure requiring heart transplant and a number of associated morbidities remain ongoing clinical challenges for these patients.

Intramyocardial cell-based therapy with Lomecel-B during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: the ELPIS phase I trial.

Aims: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation.

Methods And Results: We conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation.

Efficacy of a growth hormone-releasing hormone agonist in a murine model of cardiometabolic heart failure with preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) represents a major unmet medical need owing to its diverse pathophysiology and lack of effective therapies. Potent synthetic, agonists (MR-356 and MR-409) of growth hormone-releasing hormone (GHRH) improve the phenotype of models of HF with reduced ejection fraction (HFrEF) and in cardiorenal models of HFpEF. Endogenous GHRH exhibits a broad range of regulatory influences in the cardiovascular (CV) system and aging and plays a role in several cardiometabolic conditions including obesity and diabetes.

S-nitrosylation of CSF1 receptor increases the efficacy of CSF1R blockage against prostate cancer.

Sustained oxidative stress in castration-resistant prostate cancer (CRPC) cells potentiates the overall tumor microenvironment (TME). Targeting the TME using colony-stimulating factor 1 receptor (CSF1R) inhibition is a promising therapy for CRPC. However, the therapeutic response to sustained CSF1R inhibition (CSF1Ri) is limited as a monotherapy.

Neonatal intermittent hypoxia persistently impairs lung vascular development and induces long-term lung mitochondrial DNA damage.

Adults born preterm have an increased risk of pulmonary vascular disease. Extreme preterm infants often require supplemental oxygen but they also exhibit frequent intermittent hypoxemic episodes (IH). Here, we test the hypothesis that neonatal IH induces lung endothelial cell mitochondrial DNA (mitDNA) damage and contributes to long-term pulmonary vascular disease and pulmonary hypertension (PH).

Myocarditis following COVID-19 vaccine: incidence, presentation, diagnosis, pathophysiology, therapy, and outcomes put into perspective. A clinical consensus document supported by the Heart Failure Association of the European Society of Cardiology (ESC) and the ESC Working Group on Myocardial and Pericardial Diseases.

Over 10 million doses of COVID-19 vaccines based on RNA technology, viral vectors, recombinant protein, and inactivated virus have been administered worldwide. Although generally very safe, post-vaccine myocarditis can result from adaptive humoral and cellular, cardiac-specific inflammation within days and weeks of vaccination. Rates of vaccine-associated myocarditis vary by age and sex with the highest rates in males between 12 and 39 years.

Mouse Model of Heart Failure With Preserved Ejection Fraction Driven by Hyperlipidemia and Enhanced Cardiac Low-Density Lipoprotein Receptor Expression.

Background The pathways of diastolic dysfunction and heart failure with preserved ejection fraction driven by lipotoxicity with metabolic syndrome are incompletely understood. Thus, there is an urgent need for animal models that accurately mimic the metabolic and cardiovascular phenotypes of this phenogroup for mechanistic studies. Methods and Results Hyperlipidemia was induced in WT-129 mice by 4 weeks of biweekly poloxamer-407 intraperitoneal injections with or without a single intravenous injection of adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor (n=31), or single intravenous injection with adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor alone (n=10).

Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury.

Successful cell therapy requires cells to resist the hostile ischemic myocardium, be retained to continue secreting cardioprotective growth factors/exosomes, and resist immunological host responses. Clinically relevant stem/progenitor cells in a rodent model of acute myocardial infarction (MI) demonstrated that neonatal cardiac mesenchymal stromal cells (nMSCs) provide the most robust cardiac functional recovery. Transplanted nMSCs significantly increased the number of tissue reparative macrophages and regulatory T-cells and decreased monocyte-derived inflammatory macrophages and neutrophils in the host myocardium.

Mesenchymal Stem Cell-derived Extracellular Vesicles Prevent Experimental Bronchopulmonary Dysplasia Complicated By Pulmonary Hypertension.

Mesenchymal stem cell (MSC) extracellular vesicles (EVs) have beneficial effects in preclinical bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) models. The optimal source, dosing, route, and duration of effects are however unknown. The objectives of this study were to (a) compare the efficacy of GMP-grade EVs obtained from Wharton's Jelly MSCs (WJ-MSCs) and bone marrow (BM-MSCs), (b) determine the optimal dosing and route of administration, (c) evaluate its long-term effects, and (d) determine how MSC EVs alter the lung transcriptome.

Mice on Balb/C Background Have Less Severe Cardiorespiratory Phenotype and SGLT2 Over-Expression Compared to 129x1/SvJ and C57Bl/6 Backgrounds.

Alport syndrome (AS) is a hereditary renal disorder with no etiological therapy. In the preclinical model of AS, disease progression and severity vary depending on mouse strain. The sodium-glucose cotransporter 2 (SGLT2) is emerging as an attractive therapeutic target in cardiac/renal pathologies, but its application to AS remains untested.