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91 results match your criteria: "Medical Research Council Centre for Regenerative Medicine[Affiliation]"
Cell Genom
November 2024
Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK; National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA; RNA Therapeutics Laboratory, National Center for Advancing Translational Sciences (NCATS), NIH, Rockville, MD 20850, USA. Electronic address:
Comput Methods Programs Biomed
January 2024
Agile Tomography Group, School of Engineering, University of Edinburgh, Edinburgh, U.K.. Electronic address:
Background: Electrical impedance tomography (EIT) has gained considerable attention in the medical field for the diagnosis of lung-related diseases, owing to its non-invasive and real-time characteristics. However, due to the ill-posedness and underdetermined nature of the inverse problem in EIT, suboptimal reconstruction performance and reduced robustness against the measurement noise and modeling errors are common issues.
Objectives: This study aims to mine the deep feature information from measurement voltages, acquired from the EIT sensor, to reconstruct the high-resolution conductivity distribution and enhance the robustness against the measurement noise and modeling errors using the deep learning method.
Science
February 2022
High Definition Disease Modelling Lab, Stem Cell and Organoid Epigenetics, IEO, European Institute of Oncology, IRCCS, 20141 Milan, Italy.
Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence.
View Article and Find Full Text PDFEBioMedicine
December 2020
Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, United Kingdom. Electronic address:
Background: Extracellular microRNAs enter kidney cells and modify gene expression. We used a Dicer-hepatocyte-specific microRNA conditional-knock-out (Dicer-CKO) mouse to investigate microRNA transfer from liver to kidney.
Methods: Dicer mice were treated with a Cre recombinase-expressing adenovirus (AAV8) to selectively inhibit hepatocyte microRNA production (Dicer-CKO).
BMC Med Genomics
April 2020
Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Background: Despite the emergence of cell-free DNA (cfDNA) as a clinical biomarker in cancer, the tissue origins of cfDNA in healthy individuals have to date been inferred only by indirect and relative measurement methods, such as tissue-specific methylation and nucleosomal profiling.
Methods: We performed the first direct, absolute measurement of the tissue origins of cfDNA, using tissue-specific knockout mouse strains, in both healthy mice and following paracetamol (APAP) overdose. We then investigated the utility of total cfDNA and the percentage of liver-specific cfDNA as clinical biomarkers in patients presenting with APAP overdose.
Science
March 2020
Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK.
Proc Natl Acad Sci U S A
January 2020
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065;
Primary human hepatocytes (PHHs) are an essential tool for modeling drug metabolism and liver disease. However, variable plating efficiencies, short lifespan in culture, and resistance to genetic manipulation have limited their use. Here, we show that the pyrrolizidine alkaloid retrorsine improves PHH repopulation of chimeric mice on average 10-fold and rescues the ability of even poorly plateable donor hepatocytes to provide cells for subsequent ex vivo cultures.
View Article and Find Full Text PDFLife Sci Alliance
October 2019
UK Medical Research Council Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland
, , and encode DNA demethylases that play critical roles during stem cell differentiation and reprogramming to pluripotency. Although all three genes are transcribed in pluripotent cells, little is known about the expression of the corresponding proteins. Here, we tagged all the endogenous family alleles using CRISPR/Cas9, and characterised TET protein expression in distinct pluripotent cell culture conditions.
View Article and Find Full Text PDFHepatology
March 2020
Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
Background And Aims: Mechanisms underlying the repair of extrahepatic biliary tree (EHBT) after injury have been scarcely explored. The aims of this study were to evaluate, by using a lineage tracing approach, the contribution of peribiliary gland (PBG) niche in the regeneration of EHBT after damage and to evaluate, in vivo and in vitro, the signaling pathways involved.
Approach And Results: Bile duct injury was induced by the administration of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 14 days to Krt19 TdTomato mice.
iScience
June 2019
Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, Scotland EH16 4UU, UK. Electronic address:
During mammalian development, liver differentiation is driven by signals that converge on multiple transcription factor networks. The hepatocyte nuclear factor signaling network is known to be essential for hepatocyte specification and maintenance. In this study, we have generated deletion and point mutants of hepatocyte nuclear factor-4alpha (HNF4α) to precisely evaluate the function of protein domains during hepatocyte specification from human pluripotent stem cells.
View Article and Find Full Text PDFNat Neurosci
July 2019
Medical Research Council Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
Failed regeneration of CNS myelin contributes to clinical decline in neuroinflammatory and neurodegenerative diseases, for which there is an unmet therapeutic need. Here we reveal that efficient remyelination requires death of proinflammatory microglia followed by repopulation to a pro-regenerative state. We propose that impaired microglia death and/or repopulation may underpin dysregulated microglia activation in neurological diseases, and we reveal therapeutic targets to promote white matter regeneration.
View Article and Find Full Text PDFNat Rev Clin Oncol
August 2019
CRUK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.
Proc Natl Acad Sci U S A
May 2019
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), Immunos, 138648 Singapore;
White matter abnormalities are a nearly universal pathological feature of neurodegenerative disorders including Huntington disease (HD). A long-held assumption is that this white matter pathology is simply a secondary outcome of the progressive neuronal loss that manifests with advancing disease. Using a mouse model of HD, here we show that white matter and myelination abnormalities are an early disease feature appearing before the manifestation of any behavioral abnormalities or neuronal loss.
View Article and Find Full Text PDFNat Rev Clin Oncol
August 2019
CRUK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.
Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. In an attempt to encourage progress in our understanding and ability to successfully treat patients with brain tumours, Cancer Research UK convened an international panel of clinicians and laboratory-based scientists to identify challenges that must be overcome if we are to cure all patients with a brain tumour.
View Article and Find Full Text PDFFront Cell Neurosci
November 2018
Centre for Genomic and Regenerative Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia.
Cellular quiescence is a reversible, non-cycling state controlled by epigenetic, transcriptional and niche-associated molecular factors. Quiescence is a condition where molecular signaling pathways maintain the poised cell-cycle state whilst enabling rapid cell cycle re-entry. To achieve therapeutic breakthroughs in oncology it is crucial to decipher these molecular mechanisms employed by the cancerous milieu to control, maintain and gear stem cells towards re-activation.
View Article and Find Full Text PDFStem Cells Transl Med
March 2019
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
We describe a novel therapeutic approach for cirrhosis using mesenchymal stem cells (MSCs) and colony-stimulating factor-1-induced bone marrow-derived macrophages (id-BMMs) and analyze the mechanisms underlying fibrosis improvement and regeneration. Mouse MSCs and id-BMMs were cultured from mouse bone marrow and their interactions analyzed in vitro. MSCs, id-BMMs, and a combination therapy using MSCs and id-BMMs were administered to mice with CCl -induced cirrhosis.
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
July 2018
BioLamina, Löfströms Allé 5A, 172 66 Sundbyberg, Sweden
Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process , but less attention has been paid to the extracellular matrix used.
View Article and Find Full Text PDFJ Am Soc Nephrol
July 2018
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany;
Interstitial fibrosis is associated with chronic renal failure. In addition to fibroblasts, bone marrow-derived cells and tubular epithelial cells have the capacity to produce collagen. However, the amount of collagen produced by each of these cell types and the relevance of fibrosis to renal function are unclear.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2018
School of Life Sciences, University of Dundee, DD1 5EH Dundee, United Kingdom;
Lancet Gastroenterol Hepatol
May 2018
Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
Proc Natl Acad Sci U S A
February 2018
School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom;
For many cancer types, incidence rises rapidly with age as an apparent power law, supporting the idea that cancer is caused by a gradual accumulation of genetic mutations. Similarly, the incidence of many infectious diseases strongly increases with age. Here, combining data from immunology and epidemiology, we show that many of these dramatic age-related increases in incidence can be modeled based on immune system decline, rather than mutation accumulation.
View Article and Find Full Text PDFActa Neuropathol
June 2018
Medical Research Council Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
The most prevalent neurological disorders of myelin include perinatal brain injury leading to cerebral palsy in infants and multiple sclerosis in adults. Although these disorders have distinct etiologies, they share a common neuropathological feature of failed progenitor differentiation into myelin-producing oligodendrocytes and lack of myelin, for which there is an unmet clinical need. Here, we reveal that a molecular pathology common to both disorders is dysregulation of activin receptors and that activin receptor signaling is required for the majority of myelin generation in development and following injury.
View Article and Find Full Text PDFNPJ Regen Med
October 2017
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Regenerative medicine therapies hold enormous potential for a variety of currently incurable conditions with high unmet clinical need. Most progress in this field to date has been achieved with cell-based regenerative medicine therapies, with over a thousand clinical trials performed up to 2015. However, lack of adequate safety and efficacy data is currently limiting wider uptake of these therapies.
View Article and Find Full Text PDFCancer Res
March 2018
Centre for Cell Signalling and Inflammation, Department of Medicine, Imperial College London, London, United Kingdom.
T-cell exclusion from the tumor microenvironment (TME) is a major barrier to overcoming immune escape. Here, we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45β that restricts tumor-associated inflammation and T-cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma and ovarian adenocarcinoma, inhibition in myeloid cells restored activation of proinflammatory tumor-associated macrophages (TAM) and intratumoral immune infiltration, thereby diminishing oncogenesis.
View Article and Find Full Text PDFJ Immunol
February 2018
Medical Research Council Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative.
View Article and Find Full Text PDF