A5051490863- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Pancreatic function and diabetes
- Blood groups and transfusion
- Pluripotent Stem Cells Research
- Zebrafish Biomedical Research Applications
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Hematopoietic Stem Cell Transplantation
- Platelet Disorders and Treatments
- Single-cell and spatial transcriptomics
- Extracellular vesicles in disease
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cellular transport and secretion
- Plant responses to water stress
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- Skin and Cellular Biology Research
- Iron Metabolism and Disorders
- Genomics and Chromatin Dynamics
- Hippo pathway signaling and YAP/TAZ
- Coronary Interventions and Diagnostics
Mahidol University
2014-2024
Siriraj Hospital
2014-2024
University of Bristol
2011-2019
Bristol Institute for Transfusion Sciences
2012
At Bristol
2012
Abstract With increasing worldwide demand for safe blood, there is much interest in generating red blood cells vitro as an alternative clinical product. However, available methods generation of from adult and cord progenitors do not yet provide a sustainable supply, current systems using pluripotent stem generate viable cells. We have taken approach, immortalizing early erythroblasts stable line, which provides continuous supply The immortalized differentiate efficiently into mature,...
Cord blood stem cells are an attractive starting source for the production of red in vitro therapy because additional expansion potential compared with adult peripheral progenitors and cord banks usually being more representative national populations than donors. Consequently, it is important to establish how similar RBCs cells. In this study, we used multiplex tandem mass tag labeling combined nano-LC-MS/MS compare proteome reticulocytes. 2838 unique proteins were identified, providing most...
Report26 April 2018Open Access Transparent process Enhancement of red blood cell transfusion compatibility using CRISPR-mediated erythroblast gene editing Joseph Hawksworth School Biochemistry, University Bristol, UK Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Search more papers by this author Timothy J Satchwell NIHR Research Unit, Marjolein Meinders Deborah E Daniels Fiona Regan Imperial College Healthcare NHS Trust, London, &...
Induced pluripotent stem cells (iPSC) are an attractive progenitor source for the generation of in vitro blood products. However, before iPSC-derived erythroid can be considered therapeutic use their similarity to adult must confirmed. We have analysed proteome differentiated from iPSC fibroblast derived line (C19) and showed they express hallmark RBC proteins, including all those ankyrin 4.1R complex. next compared three lines (C19, OCE1, OPM2) with that cord progenitors. Of 1989 proteins...
A major barrier to the clinical use of erythrocytes generated in vitro from pluripotent stem cells or cord blood progenitors is failure these express adult hemoglobin. The key regulators globin switching KLF1 and BCL11A are absent at a lower level than K562 erythroid differentiated induced progenitors. Transfection transduction with either BCL11A-XL had little effect on β-globin expression. In contrast, both transcription factors stimulated Similarly, increasing cell-derived cell line...
Thalassemia is the most common genetic disease worldwide; those with severe require lifelong blood transfusion and iron chelation therapy. The definitive cure for thalassemia allogeneic hematopoietic stem cell transplantation, which limited due to lack of HLA-matched donors risk post-transplant complications. Induced pluripotent (iPSC) technology offers prospects autologous cell-based therapy could avoid immunological problems. We now report correction beta hemoglobin (HBB) gene in iPSCs...
Human induced pluripotent stem cells (hiPSCs) offer a renewable source of for the generation hematopoietic cell-based therapy, disease modeling, and drug screening. However, current serum/feeder-free differentiation protocols rely on use various cytokines, which makes process very costly or embryoid bodies (EBs), are labor-intensive can cause heterogeneity during differentiation. Here, we report simple feeder serum-free monolayer protocol efficient iPSC-derived multipotent hematoendothelial...
Abstract The β-thalassemia syndromes are the most prevalent genetic disorder globally, characterised by reduced or absent β-globin chain synthesis. HbE/β-thalassemia is a subtype of with extremely high frequency in Asia. Studying molecular defects behind severely impeded paucity material from patients and lack suitable cell lines. Approaches to derive erythroid cells induced pluripotent stem (iPSCs) created confounded poor levels expansion, aberrant incomplete differentiation...
Percutaneous coronary intervention (PCI) is a common procedure for the management of artery obstruction. However, it usually causes vascular wall injury leading to restenosis that limits long-term success PCI endeavor. The ultimate objective this study was develop targeting nanoparticles (NPs) were destined injured subendothelium and attract endothelial progenitor cells (EPCs) damaged location endothelium regeneration. Biodegradable poly(lactic-co-glycolic acid) (PLGA) NPs conjugated with...
In vitro generation of red blood cells has become a goal for scientists globally. Directly, in vitro-generated (RBCs) may close the gap between supply obtained through donation and high demand therapeutic uses. addition, can be used as model haematologic disorders to allow study their pathophysiology novel treatment discovery. For those reasons, number RBC culture systems have been established shown successful; however, cost each millilitre packed is still extremely high. order reduce cost,...
Abstract Development of in vitro culture systems for the generation red blood cells is a goal scientists globally with aim producing clinical grade products transfusion. Although mature reticulocytes can be efficiently generated by such systems, numbers produced fall short that required therapeutics, due to limited proliferative capacity erythroblasts. To overcome this hurdle, approaches are increase expansion potential systems. The OP9 mouse stromal cell line known promote haematopoietic...
Pluripotent stem cells are attractive progenitor for the generation of erythroid in vitro as have expansive proliferative potential. However, although embryonic (ESC) and induced pluripotent (iPSC) can be to undergo differentiation, majority fail enucleate molecular basis this defect is unknown. One protein that has been associated with initial phase cell enucleation intermediate filament vimentin, loss vimentin potentially required process proceed. In study, we used our established culture...
Yes-associated protein (YAP) and WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) are two key co-activators of the Hippo pathway. Both were originally characterized organ size cell proliferation regulators. Later studies demonstrated that pathway may play a role in Drosophila mammal hematopoiesis. However, human erythropoiesis has not yet been fully elucidated. The YAP TAZ was studied hematopoietic stem (HSC) lineage determination by using mobilized peripheral blood...
Human ZNF648 is a novel poly C-terminal C2H2 zinc finger (ZnF) protein identified amongst the most dysregulated proteins in erythroid cells differentiated from induced pluripotent stem cells. Its nuclear localization and structure indicate it likely DNA-binding protein. Using combination of overexpression an line primary adult cells, knockdown megakaryocytes, comparative proteomics transcriptomics we show that required for both megakaryocyte differentiation. Orthologues were detected across...
β-thalassaemia is one of the most common genetic blood diseases worldwide with over 300 mutations in HBB gene affecting red cell functions. Recently, advances genome editing technology have provided a powerful tool for precise correction. Generation patient-derived induced pluripotent stem cells (iPSCs) followed by correction and differentiation into haematopoietic stem/progenitor (HSPCs) offers potential therapy to cure disease. However, biggest challenge generate functional HSPCs that are...
2020 of Haematologica, 1 during the final processing manuscript labeling Figure 2E got accidentally inverted.On both BEL-A and HUDEP-2 graphs, γ β globin labels are wrong way around.The corrected panel E 2 is shown here.
At present, the numbers of cultured erythroid cells obtained from culture systems are not on a scale that can be used for therapeutics since have limited proliferation capacity. Stromal believed to play important roles during erythropoiesis. Our previous study shows factors secreted by stromal enhance capacity adult in system. Among identified factors, angiotensinogen is one most abundant proteins cells. This aims investigate effect angiotensin II, an derivative, cells.•The receptor II was...
Abstract Polycythaemia vera (PV) is a haematological disorder caused by an overproduction of erythroid cells. To date, the molecular mechanisms involved in disease pathogenesis are still ambiguous. This study aims to identify aberrantly expressed proteins erythroblasts PV patients utilizing mass spectrometry-based proteomic analysis. Haematopoietic stem cells (HSCs) were isolated from newly-diagnosed patients, who have received cytoreductive therapy, and healthy subjects. In vitro...