A5051016007- Pancreatic function and diabetes
- Mesenchymal stem cell research
- Diabetes and associated disorders
- Diabetes Management and Research
- Cannabis and Cannabinoid Research
- Metabolism, Diabetes, and Cancer
- Genetics and Neurodevelopmental Disorders
- Immune Cell Function and Interaction
- Tissue Engineering and Regenerative Medicine
- T-cell and B-cell Immunology
- Neonatal Respiratory Health Research
- Pancreatic and Hepatic Oncology Research
- Apelin-related biomedical research
- Pluripotent Stem Cells Research
- Autophagy in Disease and Therapy
- Axon Guidance and Neuronal Signaling
- Cytomegalovirus and herpesvirus research
University of Exeter
2021-2024
Vrije Universiteit Brussel
2023
King's College London
2010-2021
Diabetes UK
2011
King's College School
2008
The final pathway of β cell destruction leading to insulin deficiency, hyperglycemia, and clinical type 1 diabetes is unknown. Here we show that circulating CTLs can kill cells via recognition a glucose-regulated epitope. First, identified 2 naturally processed epitopes from the human preproinsulin signal peptide by elution HLA-A2 (specifically, protein encoded A*0201 allele) molecules. Processing these was unconventional, requiring neither proteasome nor transporter associated with...
Ductal cells have been proposed as a source of adult β cell neogenesis, but this has remained controversial. By combining lineage tracing, 3D imaging, and single-cell RNA sequencing (scRNA-seq) approaches, we show that ductal contribute to the population over time. Lineage tracing using Neurogenin3 (Ngn3)-CreERT line identified expressing endocrine master transcription factor Ngn3 were positive for δ marker somatostatin occasionally co-expressed insulin. The number hormone-expressing was...
Immune-mediated destruction of beta-cells resulting in type 1 diabetes involves activation proinflammatory, islet autoreactive T-cells, a process under the control dendritic cells innate immune system. We tested hypothesis that development is associated with disturbance blood cell subsets could enhance islet-specific autoimmunity.We examined (plasmacytoid and myeloid) 40 patients recent-onset (median duration 28 days) matched subjects. also relative ability different to present soluble or...
The aims of the present study were (i) to determine whether reported beneficial effects mesenchymal stromal cells (MSCs) on mouse islet function extend clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical transplantation; (ii) identify possible mechanisms through which MSCs influence function.Human islets co-cultured with adipose tissue-derived (hASCs) or pre-treated its products - extracellular matrix (ECM) annexin A1 (ANXA1). Mouse...
Pretransplant islet culture is associated with the loss of cell mass and insulin secretory function. Insulin secretion from β-cells primarily controlled by mitochondrial ATP generation in response to elevations extracellular glucose. Coculture islets mesenchymal stromal cells (MSCs) improves function vitro, which correlates superior graft vivo. This study aimed determine whether improved transfer MSCs cocultured islets. We have demonstrated human adipose coculture. Fluorescence imaging...
We have previously demonstrated that coculture of islets with mesenchymal stromal cells (MSCs) enhanced islet insulin secretory capacity in vitro, correlating improved graft function vivo. To identify factors contribute to MSC-mediated improvements function, we used an unbiased quantitative RT-PCR screening approach MSC-derived peptide ligands G-protein–coupled receptors are expressed by cells. high expression annexin A1 (ANXA1) mRNA MSCs and confirmed at the protein level lysates...
In humans, tolerance to renal transplants has been associated with alterations in B-cell gene transcription and maintenance of the numbers circulating transitional B cells. Here, we use a mouse model transplantation investigate contribution cells allograft survival. We demonstrate that transfer from mice rendered tolerant MHC class I mismatched skin grafts can prolong graft survival dose-dependent antigen-specific manner degree similar afforded by graft-specific regulatory T (Treg) Tolerance...
We have recently shown that preculturing islets with kidney-derived mesenchymal stromal cells (MSCs) improves transplantation outcome in streptozotocin-diabetic mice implanted a minimal mass of beneath the kidney capsule. In present study, we extended our previous observations to investigate whether MSCs can also be used enhance islet function at clinically intraportal site. derived from adipose tissue, which are more readily accessible than alternative sources human subjects and expanded...
Aims/hypothesis: Culture-expanded mesenchymal stromal cells (MSCs) reduce immune cell activation and improve islet functional survival. However, little is known about native human pancreatic MSCs (npMSCs) in health or how they are altered type 1 diabetes. Here, we determined the number, density islet-protective phenotype of npMSCs situ control individuals those with Methods: Multiplex immunohistochemistry was used to identify (CD90 + /CD105 /CD73 /CD31 - /CD45 /CD34 ) pancreas sections from...
We have previously shown that co-transplantation of islets and Mesenchymal Stem Cells (MSCs) improves islet graft function revascularisation, which was associated with the maintenance normal morphology. The aim current study to determine whether maintaining morphology in absence additional islet-helper cells would improve transplantation outcome diabetic mice. Islets were isolated from C57BL/6 Recipient streptozotocin-diabetic mice transplanted a minimal mass 150 as single pellet or either...
Abstract Islet transplantation has the potential to cure type 1 diabetes, but current protocols are not optimal and there is extensive loss of islet β-cell insulin secretory function during immediate post-transplantation period. Studies using experimental models diabetes have shown that coculture islets with mesenchymal stromal cells (MSCs) prior improves graft function, several variables differed among research groups (e.g., MSCs used treatment conditions). We therefore assessed effects on...
Abstract Purpose Preculturing isolated islets with Mesenchymal Stromal Cells (MSCs) improves their functional survival in vitro and subsequent transplantation outcomes vivo. The MSC secretory product Annexin A1 (ANXA1) is a key modulator of MSC-mediated improvements islet function. current study aims to determine the influence MSCs defined products, including ANXA1, on inflammatory crosstalk between Endothelial (ECs), using models clinically-preferred intraportal niche. Methods Islets were...
Abstract Aims Human islet transplantation as a therapy for type 1 diabetes is compromised by the loss of functional beta cells in immediate post‐transplantation period. Mesenchymal stromal (MSCs) and MSC‐derived secretory peptides improve outcomes rodent models diabetes. Here, we utilized mouse model human assessed effects cocktail MSC‐secreted (screened MSC‐secretome GPCRs) on survival islets. Methods islets from nine donors (Age: 36–57; BMI: 20–35) were treated with recombinant annexin A1...
Cotransplantation of islets with mesenchymal stromal cells (MSCs) has been shown to improve islet transplantation outcome. Improved glycemia in graft recipients have attributed superior revascularization, maintenance organization and morphology, a multitude immunomodulatory mechanisms. These effects are mediated by vast array soluble trophic MSC-derived factors extracellular matrix production, and/or direct cell-cell contact Most these studies used experimental sites, such as the kidney,...
In Figure 7A, the mother's AA 651 position was inadvertently mislabeled.The correct 7A appears below.The JCI regrets error.