A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration.

Background: The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT).

Objectives: This study sought to test the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions.

Pim1 Kinase Overexpression Enhances ckit Cardiac Stem Cell Cardiac Repair Following Myocardial Infarction in Swine.

Background: Pim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit cardiac stem cells (CSCs) enhances their cardioreparative properties.

Objectives: The authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI).

Methods: Human cardiac stem cells (hCSCs, n = 10), hckit CSCs overexpressing Pim1 (Pim1; n = 9), or placebo (n = 10) were delivered by intramyocardial injection to immunosuppressed Yorkshire swine (n = 29) 2 weeks after MI.

Synergistic Effects of Combined Cell Therapy for Chronic Ischemic Cardiomyopathy.

Background: Both bone marrow-derived mesenchymal stem cells (MSCs) and c-kit(+) cardiac stem cells (CSCs) improve left ventricular remodeling in porcine models and clinical trials. Using xenogeneic (human) cells in immunosuppressed animals with acute ischemic heart disease, we previously showed that these 2 cell types act synergistically.

Objectives: To more accurately model clinical applications for heart failure, this study tested whether the combination of autologous MSCs and CSCs produce greater improvement in cardiac performance than MSCs alone in a nonimmunosuppressed porcine model of chronic ischemic cardiomyopathy.

Use of mesenchymal stem cells for therapy of cardiac disease.

Despite substantial clinical advances over the past 65 years, cardiovascular disease remains the leading cause of death in America. The past 15 years has witnessed major basic and translational interest in the use of stem and precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells are widely studied, and in early stage, clinical studies show promise for repair and regeneration of cardiac tissues.

Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine with subacute ischemic cardiomyopathy.

Background: Growth hormone-releasing hormone agonists (GHRH-As) stimulate cardiac repair following myocardial infarction (MI) in rats through the activation of the GHRH signaling pathway within the heart. We tested the hypothesis that the administration of GHRH-As prevents ventricular remodeling in a swine subacute MI model.

Methods And Results: Twelve female Yorkshire swine (25 to 30 kg) underwent transient occlusion of the left anterior descending coronary artery (MI).

Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients.

Background: The role of patient age in the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial.

Objectives: This study sought to determine whether the therapeutic effect of culture-expanded MSCs persists, even in older subjects.

Methods: Patients with ICM who received MSCs via transendocardial stem cell injection (TESI) as part of the TAC-HFT (Transendocardial Autologous Cells in Ischemic Heart Failure) (n = 19) and POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) (n = 30) clinical trials were divided into 2 age groups: younger than 60 and 60 years of age and older.

Clinical research skills development program in cell-based regenerative medicine.

Cell-based therapy aimed at restoring organ function is one of the most exciting and promising areas of medical research. However, a novel intervention like cell-based therapy requires physician education and training. An increasing number of physicians untrained in regenerative medicine are using cell-based therapy to treat patients for a wide variety of chronic illnesses.

Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial.

Rationale: Although accumulating data support the efficacy of intramyocardial cell-based therapy to improve left ventricular (LV) function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including reducing fibrosis, neoangiogenesis, and neomyogenesis.

Objective: To test the hypothesis that the impact on cardiac structure and function after intramyocardial injections of autologous MSCs results from a concordance of prorecovery phenotypic effects.

Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial.

Rationale: Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown.

Objective: To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments.

Methods And Results: Biplane ventriculographic and endocardial tracings were recorded.

Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial.

Importance: Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial.

Objective: To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy.

Design, Setting, And Patients: A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013).

Myocardial infarction and intramyocardial injection models in swine.

Sustainable and reproducible large animal models that closely replicate the clinical sequelae of myocardial infarction (MI) are important for the translation of basic science research into bedside medicine. Swine are well accepted by the scientific community for cardiovascular research, and they represent an established animal model for preclinical trials for US Food and Drug Administration (FDA) approval of novel therapies. Here we present a protocol for using porcine models of MI created with a closed-chest coronary artery occlusion-reperfusion technique.

Cell-based therapy for prevention and reversal of myocardial remodeling.

Although pharmacological and interventional advances have reduced the morbidity and mortality of ischemic heart disease, there is an ongoing need for novel therapeutic strategies that prevent or reverse progressive ventricular remodeling following myocardial infarction, the process that forms the substrate for ventricular failure. The development of cell-based therapy as a strategy to repair or regenerate injured tissue offers extraordinary promise for a powerful anti-remodeling therapy. In this regard, the field of cell therapy has made major advancements in the past decade.

Mechanisms of non-fatal stent-related myocardial infarction late following coronary stenting with drug-eluting stents and bare metal stents. Insights from optical coherence tomography.

Background: A prospective observational study using optical coherence tomography (OCT) of patients with myocardial infarction (MI), late following drug-eluting (DES) or bare metal stent (BMS) implantation, when the stented segment was considered culprit.

Methods And Results: Seventeen patients (58.9±8.

Evaluation of culprit saphenous vein graft lesions with optical coherence tomography in patients with acute coronary syndromes.

Objectives: This study sought to assess, with optical coherence tomography (OCT), presumably culprit atherosclerotic lesions of saphenous vein grafts (SVGs) in patients with acute coronary syndromes (ACS).

Background: Atherosclerotic lesions of SVGs have been studied in vivo with angioscopy and intravascular ultrasound. However, imaging with OCT, which has a higher resolution than intravascular ultrasound and better penetration than angioscopy, has not been conducted systematically.

Mechanism of a reproducible accordion phenomenon: insights by optical coherence tomography visualization.

Pseudostenosis or 'accordion phenomenon' is a transient angiographic multifocal filling defect observed mostly during percutaneous coronary intervention, mainly in tortuous vessels. We describe a case of a reproducible accordion effect in the right coronary artery accompanied by only a mild clinical syndrome. Optical coherence tomography evaluation of this strange and fortunately completely reversible phenomenon is discussed.

Simultaneous drug-eluting and bare-metal stent implantation: long-term clinical outcome and findings of clinically indicated coronary angiography.

Background: Simultaneous drug-eluting stent (DES) and bare-metal stent (BMS) implantation is occasionally employed in clinical practice, but its long-term clinical and angiographic outcome is not clear.

Hypothesis: We aimed to describe the long-term clinical outcome and the findings of clinically indicated coronary angiography in patients subjected to simultaneous DES and BMS implantation ("hybrid stenting").

Methods: We identified 236 patients (mean age 62.

An optical coherence tomography study of two new generation stents with biodegradable polymer carrier, eluting paclitaxel vs. biolimus-A9.

Background: Tissue coverage and strut apposition of drug eluting stents (DES), which can be assessed with optical coherence tomography (OCT), may be associated with late stent thrombosis (LST).

Methods: Prospective observational angiographic and OCT follow-up at 6 months post-implantation of a biolimus-A9 eluting stent (BES) vs. a paclitaxel eluting stent (PES), with biodegradable polymer carriers.

Anomalous origin of the left main coronary artery from the main pulmonary artery in an elderly patient.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) syndrome is an extremely rare diagnosis in elderly patients. We describe a 73-year-old female with ALCAPA who underwent successful repair of this coronary anomaly.

Double-barrel stenting of distal left main stenosis in a patient with acute coronary syndrome: intravascular ultrasound and optical coherence tomography follow-up at six months.

A 58-year-old man presented with frequent episodes of angina at rest. A diagnosis of anterior non-ST elevation myocardial infarction was made. Coronary angiography performed on the day of admission revealed a significant stenosis (50% to 60%) of the distal left main stem (LMS) extending to the ostia of the left anterior descending and left circumflex arteries.

Neointimal coverage and stent strut apposition six months after implantation of a paclitaxel eluting stent in acute coronary syndromes: an optical coherence tomography study.

Objectives: Prospective optical coherence tomography (OCT) study of strut apposition and neointimal hyperplasia thickness (NIH) of a paclitaxel eluting stent (PES), (Infinium, Sahajanand Medical Technologies Pvt Ltd.).

Background: Few data exist concerning neointimal coverage of PES.