A5022702109- Congenital heart defects research
- Tissue Engineering and Regenerative Medicine
- Cardiac electrophysiology and arrhythmias
- Mesenchymal stem cell research
- Cardiac Fibrosis and Remodeling
- Ion channel regulation and function
- Pluripotent Stem Cells Research
- Neuroscience and Neural Engineering
- Cardiomyopathy and Myosin Studies
- Cardiovascular Function and Risk Factors
- Electrospun Nanofibers in Biomedical Applications
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- Telomeres, Telomerase, and Senescence
- Heart Rate Variability and Autonomic Control
- RNA Research and Splicing
- Cardiovascular Effects of Exercise
- Peptidase Inhibition and Analysis
- Cardiac Ischemia and Reperfusion
- Muscle Physiology and Disorders
- Cardiac Structural Anomalies and Repair
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Angiogenesis and VEGF in Cancer
New York Medical College
2015-2024
Harvard University
2010-2019
Brigham and Women's Hospital
2009-2018
Boston University
2004-2015
Men's Health Boston
2014
Institute of Molecular Bioimaging and Physiology
2013
Albert Einstein College of Medicine
2009-2013
Montefiore Medical Center
2009-2013
Beth Israel Deaconess Medical Center
2010-2013
LifeArc
2013
The identification of cardiac progenitor cells in mammals raises the possibility that human heart contains a population stem capable generating cardiomyocytes and coronary vessels. characterization (hCSCs) would have important clinical implications for management failing heart. We established conditions isolation expansion c- kit -positive hCSCs from small samples myocardium. Additionally, we tested whether these ability to form functionally competent myocardium after infarction...
To determine whether cellular aging leads to a cardiomyopathy and heart failure, markers of senescence, cell death, telomerase activity, telomere integrity, regeneration were measured in myocytes wild-type mice (WT). These parameters similarly studied insulin-like growth factor-1 (IGF-1) transgenic (TG) because IGF-1 promotes survival may delay aging. Importantly, the consequences on cardiac stem (CSC) senescence evaluated. Gene products implicated arrest such as p27 Kip1 , p53, p16 INK4a...
Cardiac stem cells and early committed (CSCs-ECCs) express c-Met insulin-like growth factor-1 (IGF-1) receptors synthesize secrete the corresponding ligands, hepatocyte factor (HGF) IGF-1. HGF mobilizes CSCs-ECCs IGF-1 promotes their survival proliferation. Therefore, were injected in hearts of infarcted mice to favor, respectively, translocation from surrounding myocardium dead tissue viability these within damaged area. To facilitate migration homing infarct, a gradient was introduced...
The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected a 90-min coronary occlusion; at 4 h reperfusion, CSCs the arteries via catheter positioned into aortic root. Echocardiographic analysis showed that injection attenuated increase in left ventricular (LV) end-diastolic dimensions and impairment LV systolic performance 5 weeks infarction....
Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to differentiate into myocytes and coronary vessels. The claim has also been made that BMCs acquire a cell phenotype different from blood lineages only by fusing with resident cells. Technical problems exist induction myocardial infarction successful injection mouse heart. Similarly, accurate analysis populations implicated regeneration dead tissue is complex these factors together may account for negative...
Cardiac stem cells (CSCs) have been identified in the adult heart, but microenvironment that protects slow-cycling, undifferentiated, and self-renewing CSCs remains to be determined. We report myocardium possesses interstitial structures with architectural organization of cell niches harbor long-term BrdU-retaining cells. The recognition label-retaining provides functional evidence resident myocardium, indicating heart is an organ regulated by a compartment. contain lineage-committed cells,...
Although progenitor cells have been described in distinct anatomical regions of the lung, description resident stem has remained elusive.Surgical lung-tissue specimens were studied situ to identify and characterize human lung cells. We defined their phenotype functional properties vitro vivo.Human lungs contain undifferentiated nested niches distal airways. These are self-renewing, clonogenic, multipotent vitro. After injection into damaged mouse vivo, form bronchioles, alveoli, pulmonary...
Diabetes leads to a decompensated myopathy, but the etiology of cardiac disease is poorly understood. Oxidative stress enhanced with diabetes and oxygen toxicity may alter progenitor cell (CPC) function resulting in defects CPC growth myocyte formation, which favor premature myocardial aging heart failure. We report that model insulin-dependent mellitus, generation reactive species (ROS) telomeric shortening, expression senescent associated proteins p53 p16INK4a, apoptosis CPCs, impairing...
RETRACTION This article has been retracted: Circ Res . 2018;123:e00. DOI: 10.1161/RES.0000000000000246
The possibility that adult bone marrow cells (BMCs) retain a remarkable degree of developmental plasticity and acquire the cardiomyocyte lineage after infarction has been challenged, notion BMC transdifferentiation questioned. center controversy is lack unequivocal evidence in favor myocardial regeneration by injection BMCs infarcted heart. Because interest cell-based therapy for heart failure, several approaches including gene reporter assay, genetic tagging, cell genotyping, PCR-based...
RETRACTION This article has been retracted: Circ Res . 2018;123:e00. DOI: 10.1161/RES.0000000000000247
Ischemic heart disease is characterized chronically by a healed infarct, foci of myocardial scarring, cavitary dilation, and impaired ventricular performance. These alterations can only be reversed replacement scarred tissue with functionally competent myocardium. We tested whether cardiac progenitor cells (CPCs) implanted in proximity infarcts or resident CPCs stimulated locally hepatocyte growth factor insulin-like factor-1 invade the myocardium generate myocytes coronary vessels improving...
Background— Anthracyclines are the most effective drugs available in treatment of neoplastic diseases; however, they have profound consequences on structure and function heart, which over time cause a cardiomyopathy that leads to congestive heart failure. Methods Results— Administration doxorubicin rats led dilated myopathy, failure, death. To test whether effects cardiac anatomy were mediated by alterations progenitor cells (CPCs), these exposed anthracycline, increased formation reactive...
Relevant preclinical models are necessary for further mechanistic and translational studies of c-kit+ cardiac stem cells (CSCs). The present study was undertaken to determine whether intracoronary CSCs beneficial in a porcine model chronic ischemic cardiomyopathy.Pigs underwent 90-minute coronary occlusion followed by reperfusion. Three months later, autologous (n=11) or vehicle (n=10) were infused into the infarct-related artery. At this time, all indices left ventricular (LV) function...
Background— Cardiac progenitor cells (CPCs) possess the insulin-like growth factor-1 (IGF-1)-IGF-1 receptor system, and IGF-1 can be tethered to self-assembling peptide nanofibers (NF-IGF-1), leading prolonged release of this factor myocardium. Therefore, we tested whether local injection clonogenic CPCs NF-IGF-1 potentiates activation differentiation delivered resident enhancing cardiac repair after infarction. Methods Results— Myocardial infarction was induced in rats, untreated infarcts...
RETRACTION This article has been retracted: Circulation . 2019;139:e1. DOI: 10.1161/CIR.0000000000000644
Primitive cells capable of generating small resistance arterioles and capillary structures in the injured myocardium have been identified repeatedly. However, these do not form large conductive coronary arteries that would important implications management ischemic heart. In current study, we determined whether human heart possesses a class progenitor regulates growth endothelial (ECs) smooth muscle (SMCs) vasculogenesis. The expression vascular growth-factor receptor 2 (KDR) was used,...
The Notch receptor mediates cell fate decision in multiple organs. In the current work we tested hypothesis that Nkx2.5 is a target gene of Notch1 and raised possibility regulates myocyte commitment adult heart. Cardiac progenitor cells (CPCs) niches express receptor, supporting exhibit ligand Jagged1. nuclear translocation intracellular domain (N1ICD) up-regulates CPCs promotes formation cycling myocytes vitro . N1ICD RBP-Jk form protein complex, which turn binds to promoter initiating...
Heart failure is the leading cause of death in elderly, but whether this result a primary aging myopathy dictated by depletion cardiac progenitor cell (CPC) pool unknown. Similarly, current lifespan reflects ineluctable genetic clock or heart interferes with genetically determined fate organ and organism an important question. We have identified that chronological age leads to telomeric shortening CPCs, which necessity generate differentiated progeny rapidly acquires senescent phenotype...
Coronary artery disease is the most common cause of cardiac failure in Western world, and to date there no alternative bypass surgery for severe coronary atherosclerosis. We report that c-kit-positive progenitor cells (CPCs) activated with insulin-like growth factor 1 hepatocyte before their injection proximity site occlusion left rats, engrafted within host myocardium forming temporary niches. Subsequently, CPCs divided differentiated into endothelial smooth muscle and, a lesser extent,...