Abstract Myocardial dysfunction after Fontan palliation for univentricular congenital heart disease is a challenging clinical problem. The medical treatment has a limited impact, with cardiac transplant being the ultimate management step. Cell-based therapies are evolving as a new treatment for heart failure. Phase 1 clinical trials using regenerative therapeutic strategies in congenital heart disease are ongoing. We report the first case of autologous bone marrow–derived mononuclear cell administration for ventricular dysfunction, 23 years after Fontan operation in a patient with hypoplastic left heart syndrome. The cells were delivered into the coronary circulation by cardiac catheterization. Ventricular size decreased and several parameters reflecting ventricular function improved, with maximum change noted 3 months after cell delivery. Such regenerative therapeutic options may help in delaying and preventing cardiac transplant.
We performed a retrospective review of outcomes after heart transplantation during long-term follow-up of a surgical cohort of 1138 Fontan patients who were followed at the Mayo Clinic. Follow-up information was obtained from medical records and a clinical questionnaire that was mailed to patients not known to be deceased at the initiation of the study. Forty-four of 1138 Fontan patients with initial or subsequent evaluation at Mayo had cardiac transplantation between 1988 and 2014 (mean age at ...
Abstract Objectives Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS). Methods In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control grou...
Abstract Background Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation. Objectives The goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in human sub...
The current standard of care for neonates with hypoplastic left heart syndrome (HLHS) includes a series of cardiac operations culminating in a complete cavopulmonary connection. Given the increased workload placed on the right ventricle, development of ventricular dysfunction and heart failure are concerns. As this patient population ages, many may require cardiac transplantation. Cellbased strategies to treat heart failure in adults have been reported, but little is known about their feasibilit...
Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with HLHS. Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8 ± 1.5 years) were prospectively assigned to rec...
Rationale: Autologous bone marrow–derived or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials, but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is the key toward improving clinical outcomes. Objective: To determine the mechanism by which novel bone-derived stem cells support the injured heart. Methods and Results: Cortical bone–derived stem cells (CBSCs) and cardiac-de...
Background In patients with acute myocardial infarction (AMI), the number of transplanted autologous bone-marrow cells (BMC) has been linked to improvement in left ventricular ejection fraction (LVEF). Complete obstruction of myocardial microvasculature is indicated by microvascular obstruction (MO) in cardiac magnetic resonance imaging (CMR). We analyzed whether the number of transplanted cells and presence of MO were associated with improved LVEF in the double-blind, placebo-controlled, random...
Dilated cardiomyopathy is a serious problem in pediatric cardiology. Despite the relatively low incidence, the mortality is high. The conservative therapy does not improve the prognosis, and possibilities of heart transplantation are limited. There are multiple trials of use of stem cells for ischemic heart disease in the adult population. This allows us to believe that the method has perspectives in pediatric cardiology. We performed the cell therapy for seven patients, six of them had complete...
Last. Joseph C. Wu(Stanford University)H-Index: 123
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Rationale: CD34 + transplantation in dilated cardiomyopathy (DCM) was associated with short-term improvement in LVEF and exercise tolerance. Objective: We investigated long-term effects of intracoronary CD34 + cell transplantation in DCM and the relationship between intramyocardial cell homing and clinical response. Methods and Results: Of 110 DCM patients, 55 were randomized to receive CD34 + cell transplantation (SC group), and 55 received no cell therapy (controls). In SC group, CD34 + cells ...
Abstract null null Background null The rise of investigative and commercially available cell therapy products adds a new dynamic to academic medical centers; that is, the management of patient-specific cell products. The scope of cell therapy has rapidly expanded beyond in-house collection and infusion of cell products such as bone marrow and peripheral blood transplant. The complexities and volumes of cell therapies are likely to continue to become more demanding. As patient-specific “living dr...
Abstract Background Aims Viral vectors are commonly used to introduce chimeric antigen receptor (CAR) constructs into cell therapy products for the treatment of human disease. They are efficient at gene delivery and integrate into the host genome for subsequent replication but also carry risks if replication-competent lentivirus (RCL) remains in the final product. An optimal CAR T-cell product should contain sufficient integrated viral material and no RCL. Current product testing methods include...
Though the current staged surgical strategy for palliation of single ventricle heart disease, culminating in a Fontan circulation, has increased short-term survival, mounting evidence has shown that the single ventricle, especially a morphologic right ventricle (RV), is inadequate for long-term circulatory support. In addition to high rates of ventricular failure, high central venous pressures (CVP) lead to liver fibrosis or cirrhosis, lymphatic dysfunction, kidney failure, and other comorbiditi...
#1John Martinez(University of Texas at Austin)H-Index: 1
#2Sarah Zoretic(University of Texas at Austin)H-Index: 1
Last. Alvaro Moreira(University of Texas at Austin)H-Index: 12
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Adult clinical trials have reported safety and the therapeutic potential of stem cells for cardiac disease. These observations have now translated to the pediatric arena. We conducted a meta-analysis to assess safety and efficacy of cell-based therapies in animal and human studies of pediatric heart disease. A literature search was conducted to examine the effects of cell-based therapies on: (i) safety and (ii) cardiac function. In total, 18 pre-clinical and 13 human studies were included. Pre-c...
Last. Markus Krane(TUM: Technische Universität München)H-Index: 25
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The treatment of congenital heart diseases (CHDs) has improved tremendously over the last decades leading to an increasing life expectancy of this particular population. Physicians now have a broad range of therapeutic option: medical therapy, interventional procedures, or surgery. Nevertheless, shortcomings remain. The ongoing developments in regenerative medicine pave the way toward a new area in the management of CHD, especially regarding surgical intervention. Patients with CHD have a very s...