A5103074706- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Cardiac Structural Anomalies and Repair
- Pluripotent Stem Cells Research
- Cardiovascular Function and Risk Factors
- Congenital heart defects research
- Cardiac Fibrosis and Remodeling
- Adipose Tissue and Metabolism
- Electrospun Nanofibers in Biomedical Applications
- Cardiomyopathy and Myosin Studies
- Transplantation: Methods and Outcomes
- Nutrition and Health in Aging
- Mitochondrial Function and Pathology
- Cardiac pacing and defibrillation studies
- Heart Failure Treatment and Management
- Cardiovascular Effects of Exercise
- Sirtuins and Resveratrol in Medicine
- Frailty in Older Adults
- Respiratory Support and Mechanisms
- Cardiac Ischemia and Reperfusion
- Hepatitis C virus research
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Neurogenetic and Muscular Disorders Research
- Electrolyte and hormonal disorders
Bristol-Myers Squibb (Germany)
2024
University of Miami
2011-2022
AR2i
2021
Stem Cell Institute
2011-2017
Canadian Asian Studies Association
2013-2016
Miami Transplant Institute
2014-2016
Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist chronic nonischemic dilated cardiomyopathy (NIDCM).The authors conducted a randomized comparison of safety and efficacy autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs NIDCM.Thirty-seven patients were to either allo- or auto-hMSCs 1:1 ratio. Patients recruited between December 2011 July 2015 at the University Miami Hospital. received (100 million) by...
Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal cells (allo-hMSCs) exert immunomodulatory effects promote tissue repair. This a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) frailty. The primary endpoint was incidence treatment-emergent serious adverse events (TE-SAEs) at...
Although nitric oxide (NO) signaling promotes differentiation and maturation of endothelial progenitor cells, its role in the mesenchymal stem cells (MSCs) into remains controversial. We tested NO MSCs derived from WT mice homozygous for a deletion S -nitrosoglutathione reductase (GSNOR −/− ), denitrosylase that regulates -nitrosylation. GSNOR exhibited markedly diminished capacity vasculogenesis an vitro Matrigel tube–forming assay vivo relative to MSCs. This decrease was associated with...
Both cardiac myocytes and stem cells (CSCs) express the receptor of growth hormone releasing (GHRH), activation which improves injury responses after myocardial infarction (MI). Here we show that a GHRH-agonist (GHRH-A; JI-38) reverses ventricular remodeling enhances functional recovery in setting chronic MI. This response is mediated entirely by GHRH (GHRHR), as demonstrated use highly selective antagonist (MIA-602). One month MI, animals were randomly assigned to receive: placebo, GHRH-A...
Mesenchymal stem cells (MSCs) attenuate lung injury in experimental models of bronchopulmonary dysplasia (BPD). Stromal derived factor-1 (SDF-1), a chemokine secreted by MSCs, modulates angiogenesis and cell recruitment. Here we tested the hypothesis that SDF-1 mediates MSC protective effects BPD modulating angiogenesis. was knocked down MSCs using lentiviral vectors carrying anti-SDF-1 short hairpin RNA (MSC-SDF KD). Non-silencing used as control (MSC-NS control). Newborn rats exposed to...
Significance Stem cell therapy is an emerging approach to the treatment of heart failure. Endogenous or transplanted stem cells have limited repair capacity due damage by exposure stress. Agonists growth hormone-releasing hormone receptor (GHRH-R) been previously shown increase number endogenous cardiac (CSCs) after myocardial infarction; enhance vasculogenesis mesenchymal cells; and improve growth, engraftment, survival pancreatic islets in experimental models. This study shows that CSCs...
Mavacamten, a cardiac myosin inhibitor, significantly improved symptoms and function vs. placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) EXPLORER-HCM. However, the efficacy safety profiles of mavacamten Japanese are unclear.
The proto-oncogene c-Myc is vital for vascular development and promotes tumor angiogenesis, but the mechanisms by which it controls blood vessel growth remain unclear. In present work we investigated effects of knockdown in endothelial cell functions essential angiogenesis to define its role vasculature. We provide first evidence that reduction expression cells leads a pro-inflammatory senescent phenotype, features typically observed during aging pathologies associated with dysfunction....
Ischemic cardiomyopathy (ICM) and dilated (DCM) differ in histopathology prognosis. Although transendocardial delivery of mesenchymal stem cells is safe provides cardiovascular benefits both, a comparison cell efficacy ICM versus DCM has not been done.
Significance This randomized, blinded study used rigorous hemodynamic tools to test the efficacy of a synthetic growth hormone-releasing hormone agonist (GHRH‐A) on restoration diastolic function in large animal model chronic kidney disease (CKD)-induced heart failure with preserved ejection fraction (HFpEF). CKD was produced Yorkshire swine by performing 5/6 nephrectomy via catheter-based renal artery embolization. HFpEF evident at 12 wk postembolization. Daily injection GHRH-A improved...
BackgroundNon-ischemic dilated cardiomyopathy (NIDCM) responds variably to intramyocardial injection of mesenchymal stem cells (MSCs). We hypothesized that NIDCM genotype may influence responsiveness MSC therapy and performed genotyping on all patients in the POSEIDON-DCM trial.MethodsPOSEIDON-DCM (n = 34) underwent genetic sequence analysis deletion/duplication testing. The results were classified as positive for pathological variants (PV+; n 8), negative any (V−; 6), or uncertain...
Cardiac stem cells (CSCs) are being evaluated for their efficacy in the treatment of heart failure. However, numerous factors impair exogenously delivered cells' regenerative capabilities. Hypoxia is one stress that contributes to inadequate tissue repair. Here, we tested hypothesis hypoxia impairs cell proliferation, survival, and migration human CSCs relative physiological room air oxygen concentrations. Human endomyocardial biopsy-derived were isolated, selected c-Kit expression, expanded...
Abstract Aims Sex differences impact the occurrence, presentation, prognosis, and response to therapy in heart disease. Particularly, phenotypic presentation of patients with non-ischaemic dilated cardiomyopathy (NIDCM) differs between men women. However, whether mesenchymal stem cell (MSC) is influenced by sex remains unknown. We hypothesize that males females NIDCM respond similarly MSC therapy. Methods results Male (n = 24) female 10) from POSEIDON-DCM trial who received MSCs via...
Abstract Cardiac progenitor cells (CPCs) have been shown to promote cardiac regeneration and improve heart function. However, evidence suggests that their regenerative capacity may be limited in conditions of severe hypoxia. Elucidating the mechanisms involved CPC protection against hypoxic stress is essential maximize cardioprotective therapeutic potential. We investigated effects on CPCs found significant reduction proliferation impairment vasculogenesis, which were associated with...
Abstract Background Left ventricular hypertrophy and heart failure with preserved ejection fraction (HFpEF) are primary manifestations of the cardiorenal syndrome in patients chronic kidney disease (CKD). Therapies that improve morbidity mortality HFpEF lacking. Cell-based therapies promote cardiac repair ischemic non-ischemic cardiomyopathies. We hypothesized cell-based therapy ameliorates CKD-induced HFpEF. Methods Results Yorkshire pigs (n = 26) underwent 5/6 embolization-mediated...
Background: Adult cardiac stem cells (CSCs) capable of self-renewal and differentiation into cardiac, smooth muscle endothelial lineages have been shown to promote tissue repair after ischemic injury improve heart function. Despite their potential role in regeneration, evidence suggests that resident CSCs are impaired conditions such as myocardial infarction, limiting regenerative capacity. Methods Results: The growth rate is significantly reduced by 40% (p<0.05) under hypoxic stress...
Background: Our group has previously shown that growth hormone releasing receptor agonists (GHRHR-A) improve cardiac performance in heart failure models and reverse remodeling. This effect was associated with an increase the number of c-kit+ stem cells (CSCs), suggesting this agonist might have on these cells. Methods Results: We investigated expression GHRH (GHRHR) CSCs different species by flow cytometry analysis. GHRH-R is expressed 96-98% isolated from mouse, rat porcine. Results were...