A5060150579- Mesenchymal stem cell research
- Hematopoietic Stem Cell Transplantation
- Angiogenesis and VEGF in Cancer
- Neonatal Respiratory Health Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Blood Coagulation and Thrombosis Mechanisms
- T-cell and B-cell Immunology
- Respiratory Support and Mechanisms
- Blood groups and transfusion
- Monoclonal and Polyclonal Antibodies Research
- Nanoplatforms for cancer theranostics
- Pancreatic function and diabetes
- 3D Printing in Biomedical Research
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Vascular Tumors and Angiosarcomas
- Erythrocyte Function and Pathophysiology
- Acute Myeloid Leukemia Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Blood disorders and treatments
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Radiopharmaceutical Chemistry and Applications
NHS Blood and Transplant
2013-2024
Barnsley Hospital
2024
John Radcliffe Hospital
2007-2023
National Health Service
2007-2023
Mount Vernon Cancer Centre
2012
Engineering and Physical Sciences Research Council
2012
Institute of Cancer Research
2012
Royal Marsden Hospital
2012
Cancer Research UK
2009
University of Oxford
2005-2009
Abstract Purpose: The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to VDA attenuates revascularization surviving rim and thus significantly increases antitumor activity. Experimental Design: Patients with advanced solid malignancies received CA4P at 45, 54, or 63 mg/m2 on day 1, 8, then every 14 days. Bevacizumab 10 mg/kg was given 8 subsequent...
Significance Statement Mesenchymal stromal cells (MSCs) may offer a novel therapy for diabetic kidney disease (DKD), although clinical translation of this approach has been limited. The authors present findings from the first, lowest dose cohort 16 adults with type 2 diabetes and progressive DKD participating in randomized, placebo-controlled, dose-escalation phase 1b/2a trial next-generation bone marrow–derived, anti-CD362 antibody–selected allogeneic MSCs (ORBCEL-M). A single intravenous...
Cell-based regenerative medicine therapies are now frequently tested in clinical trials. In many conditions, cell administered systemically, but there is little understanding of their fate, and adverse events often under-reported. Currently, it only possible to assess safety fate preclinical studies, specifically by monitoring animals longitudinally using multi-modal imaging approaches. Here, a suite vivo modalities explore the range human murine cells, we investigate how route...
Abstract Purpose: Copper chelation reduces the secretion of many angiogenic factors and tumor growth microvascular density in animal models. ATN-224 is a second-generation analogue ammonium tetrathiomolybdate. The aim our phase I study was to reduce serum copper levels, as measured by ceruloplasmin, 5 15 mg/dL (normal 16-60) 14 21 days, determine pharmacokinetic profile evaluate dose-limiting toxicities. Patients Methods: Cohorts patients were treated with escalating oral doses until...
Bone marrow-derived endothelial progenitor cells (EPCs) have been detected in the peripheral blood of patients following thermal injury. EPCs migrate to sites active neovascularization response mediators released after trauma, contributing wound healing. The aim was characterize levels and kinetics burned patients, then relate these key mobilizing factors, vascular growth factor (VEGF) chemokine (C-X-C motif) ligand 12 (CXCL 12), compare them with those healthy subjects.The study included 19...
Vascular disrupting agents (VDA) cause acute shutdown of abnormal established tumor vasculature, followed by massive intratumoral hypoxia and necrosis. However, a viable rim tissue invariably remains from which regrowth rapidly resumes. We have recently shown that an systemic mobilization homing bone marrow-derived circulating endothelial precursor (CEP) cells could promote following treatment with either VDA or certain chemotherapy drugs. The molecular mediators this reactive host process...
Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C is a population CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety feasibility patients with moderate severe ARDS.REALIST was an open label, dose escalation which cohorts mechanically ventilated ARDS received increasing doses (100, 200 or 400 × 106 cells) single intravenous infusion...
Rationale: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in COVID-19-related Acute Respiratory Distress Syndrome (ARDS). Objectives: We investigated safety and efficacy of ORBCEL-C (CD362-enriched, umbilical cord-derived MSCs) COVID-related ARDS. Methods: This multicentre, randomised, double-blind, allocation concealed, placebo-controlled trial (NCT03042143) randomised patients with moderate-to-severe ARDS to receive (400million cells) or placebo...
Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation. Although UCB often collected from unrelated donors, directed umbilical (DCB) sibling donors also provides This report summarizes the experience in collection, testing, storage, and transplantation DCB units by National Blood Service England North Wales over 10 years. Eligibility collection was based on existing suffering a disease that may be treated cell or family history could result birth...
Hematopoietic stem cell gene therapy (HSCGT) is a promising therapeutic strategy for the treatment of neurodegenerative, metabolic disorders. The approach involves
Revascularization of the damaged tissue is pivotal to repair. Here, by bringing together two in vitro model systems, we have been able examine (1) ability human umbilical vein endothelial cells (HUVEC) containing a complete hierarchy progenitors derived from cord generate vascular tubules within stromal niche and (2) effects exposure low oxygen tensions on progenitor cell proliferation tubule formation vitro. Our results demonstrate that high proliferative potential colony forming (HPP-ECFC)...
3550 Background: The vascular disruptive agent (VDA) CA4P induces significant tumor necrosis as a single agent. Vascular shut down is reversible and tumors can re-grow due to vascularisation of the surviving rim. Pre-clinical models have demonstrated that addition an anti-VEGF antibody VDA significantly increases anti-tumor activity. Methods: Patients with advanced solid malignancies received at 45mg/m2 (cohort 1), 54mg/m2 2) or 63mg/m2 3) every 14 days followed by bevacizumab 10mg/kg 4...
Circulating endothelial cells (CECs) and progenitor (EPCs) are thought to play an important role in the vascularization of damaged tissues cancers. These also required for tissue-engineered blood vessels help skin substitutes revascularize more efficiently. A standard approach phenotyping enumeration CEC EPC is key development new therapies, identification biomarkers within that regulate their levels may be treatment cancer. We have devised improved multiparameter flow cytometric assay...
As umbilical cord blood (UCB) is a rich source of endothelial colony-forming cells (ECFC), our aim was twofold: (1) to examine potential obstetric selection criteria for achieving the highest ECFC yields from UCB units, and (2) determine whether transient storage temperatures fresh cryopreservation units affected yield function. quality assessed before after by their clonogenic proliferative potential. Of 20 factors examined, placental weight only statistically significant factor that...
<b>Background:</b> Reports of differential mutagen sensitivity conferred by a defect in the mismatch repair (MMR) pathway are inconsistent their conclusions. Previous studies have investigated cells established from immortalised human colorectal tumour lines or animal models. <b>Methods:</b> We examined primary MSH2-deficient neonatal cells, bearing biallelic truncating mutation <i>MSH2</i>, for viability and chromosomal damage after exposure to DNA-damaging agents. <b>Results:</b> exhibit...
The concentrations of interferon-alpha (IFN-alpha) in supernatants from cultures Epstein-Barr virus (EBV) transformed B-lymphoblastoid cell lines derived seven patients with congenital dyserythropoietic anaemia (CDA) type I were below the 95% confidence limits for those six healthy subjects. In contrast, IFN-alpha EBV-transformed lymphoblastoid four other types CDA and hereditary sideroblastic normal. Supernatants peripheral blood lymphocytes stimulated phytohaemagglutinin or pokeweed...
Abstract Background Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced Good Manufacturing Practice standards, patients with moderate severe COVID-19 other causes. Methods Phase 1 is multicentre open-label dose-escalation pilot trial. Patients will receive single infusion REALIST ORBCEL-C (100 × 10 6 cells, 200 or 400 cells)...