A5090189998- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Cardiomyopathy and Myosin Studies
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- Immune cells in cancer
- Tissue Engineering and Regenerative Medicine
- Neuroscience and Neural Engineering
- Atherosclerosis and Cardiovascular Diseases
- Endodontics and Root Canal Treatments
- Congenital heart defects research
- Mesenchymal stem cell research
- Dental materials and restorations
- Acute Myocardial Infarction Research
- Hematopoietic Stem Cell Transplantation
- Bone Tissue Engineering Materials
- Coronary Interventions and Diagnostics
- Additive Manufacturing and 3D Printing Technologies
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Adipokines, Inflammation, and Metabolic Diseases
- Proteoglycans and glycosaminoglycans research
- Erythropoietin and Anemia Treatment
- Inflammatory Biomarkers in Disease Prognosis
- Cell Image Analysis Techniques
University of East Anglia
2018-2025
Norwich Research Park
2018-2024
University of Houston
2024
Norfolk and Norwich University Hospital
2023
University of Nottingham
2014-2020
University of Birmingham
1945-2015
University of Colorado Denver
1962-2009
University of Florida
2005
Oregon Health & Science University
1990
Penrose Hospital
1983
Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic opened a new era safety pharmacology. Nevertheless, predictive using hPSC-CMs contrasts almost total success. Since this likely relates...
Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity model, add clarity to, HCM. CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-β-myosin heavy chain (MHC)] in 3 independent hPSC lines. Isogenic sets were differentiated...
Significance How blood stem cells within the bone marrow respond to infection is still unclear. Here we study if mitochondrial transfer from stromal required for rapid generation of leukocytes which are immune system bacterial infection. We find that mitochondria transferred 2 h sensing and show direct contact between occur. The metabolic changes follow into hematopoietic underpin mammalian response Finally, that, blocked, an increase in colonization occurs.
This study evaluated the accuracy and safety of two continuous glucose monitoring (CGM) systems, SEVEN (DexCom, San Diego, CA) Navigator (Abbott Diabetes Care, Alameda, CA), with YSI laboratory measurements blood (blood meter manufactured by YSI, Yellow Springs, OH), when worn concurrently in adults type 1 diabetes.Fourteen subjects diabetes, 33 +/- 6 (mean SD) years old, were enrolled this study. All wore both sensors over three consecutive 5-day CGM sessions (15-day wear). On Days 5, 10,...
A scalable and cost-effective synthetic polymer substrate that supports robust expansion subsequent multilineage differentiation of human pluripotent stem cells (hPSCs) with defined commercial media is presented. This can be applied to common cultureware used off-the-shelf after long-term storage. Expansion hPSCs are performed entirely on the polymeric surface, enabling clinical potential hPSC-derived realized.
Hypertrophic cardiomyopathy (HCM) is a primary disorder of contractility in heart muscle. To gain mechanistic insight and guide pharmacological rescue, this study models HCM using isogenic pairs human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the E99K-ACTC1 cardiac actin mutation. In both 3D engineered tissues 2D monolayers, arrhythmogenesis was evident all hiPSC-CMs. Aberrant phenotypes were most common hiPSC-CMs produced from heterozygote father....
Hypertrophic cardiomyopathy (HCM) is a prevalent and complex cardiovascular condition. Despite being strongly associated with genetic alterations, wide variation of disease penetrance, expressivity hallmarks progression complicate treatment. We aimed to characterize different human isogenic cellular models HCM bearing patient-relevant mutations clarify causation mechanisms, hence facilitating the development effective therapeutics.We directly compared p.β-MHC-R453C p.ACTC1-E99K...
Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo during human pluripotent stem cell differentiation (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2+/−) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, ECM gene dysregulation. In...
Small nucleolar RNAs (snoRNAs) are emerging as important regulators of cardiovascular (patho)biology. Several roles snoRNAs have recently been identified in heart development and congenital diseases, well their dynamic regulation hypertrophic dilated cardiomyopathies, coronary disease (CHD), myocardial infarction (MI), cardiac fibrosis, failure. Furthermore, reports changes vesicular snoRNA expression altered levels circulating response to stress suggest that also function signaling...
Chemically diverse polymer microarrays as a powerful screening tool for the discovery of new materials variety applications.
Hypertrophic cardiomyopathy (HCM) is characterised by increased left ventricular wall thickness that can lead to devastating conditions such as heart failure and sudden cardiac death. Despite extensive study, the mechanisms mediating many of associated clinical manifestations remain unknown human models are required. To address this, induced pluripotent stem cell (hiPSC) lines were generated from patients with a HCM mutation (c.ACTC1G301A) isogenic controls created correcting using...
<ns4:p><ns4:bold>Background:</ns4:bold> Diseases such as hypertrophic cardiomyopathy (HCM) can lead to severe outcomes including sudden death. The generation of human induced pluripotent stem cell (hiPSC) reporter lines be useful for disease modelling and drug screening by providing physiologically relevant <ns4:italic>in vitro</ns4:italic> models disease. <ns4:italic>AAVS1</ns4:italic> locus is cited a safe harbour that permissive stable transgene expression, hence favoured creating gene...
<ns4:p><ns4:bold>Background:</ns4:bold> Diseases such as hypertrophic cardiomyopathy (HCM) can lead to severe outcomes including sudden death. The generation of human induced pluripotent stem cell (hiPSC) reporter lines be useful for disease modelling and drug screening by providing physiologically relevant <ns4:italic>in vitro</ns4:italic> models disease. <ns4:italic>AAVS1</ns4:italic> locus is cited a safe harbour that permissive stable transgene expression, hence favoured creating gene...
Smith JG, AJ, Shelton RM, Cooper PR. Antibacterial activity of dentine and pulp extracellular matrix extracts. International Endodontic Journal , 45 749–755, 2012. Abstract Aim To determine whether (ECM) preparations from (pECM) (dECM) possess antimicrobial activity. Methodology Dentine ECM were isolated with 10% ethylenediaminetetraacetic acid (EDTA), pH 7.2 sequential use 0.5 mol L −1 NaCl, 11.7 0.1 tartaric acid, 2.0, respectively, protease inhibitor inclusion throughout. Antimicrobial...
There is emerging recognition of the importance a physiologically relevant in vitro cell culture environment to promote maintenance stem cells for tissue engineering and regenerative medicine purposes. In vivo, appropriate cellular cues are provided by local extracellular matrix (ECM), these not currently recapitulated well using traditional cultureware. We therefore hypothesized that better replication vivo differentiation could be achieved culturing dental pulp with their associated ECM....