A5016546207- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Biomedical Ethics and Regulation
- Tissue Engineering and Regenerative Medicine
- Additive Manufacturing and 3D Printing Technologies
- Renal and related cancers
- DNA Repair Mechanisms
- Advanced biosensing and bioanalysis techniques
- Autophagy in Disease and Therapy
- Genomic variations and chromosomal abnormalities
- Manufacturing Process and Optimization
- Congenital gastrointestinal and neural anomalies
- Congenital Anomalies and Fetal Surgery
- Neuroscience and Neural Engineering
- Retinal Development and Disorders
- Liver physiology and pathology
- Intestinal Malrotation and Obstruction Disorders
- Xenotransplantation and immune response
- Animal Genetics and Reproduction
University of Sheffield
2007-2025
MRC Centre for Regenerative Medicine
2024
Roslin Institute
2006-2008
Abstract The potential to differentiate human embryonic stem cells (hESCs) in vitro provide an unlimited source of hepatocytes for use biomedical research, drug discovery, and the treatment liver diseases holds great promise. Here we describe a three-stage process efficient reproducible differentiation hESCs by priming towards definitive endoderm with activin A sodium butyrate prior further dimethyl sulfoxide, followed maturation hepatocyte growth factor oncostatin M. We have demonstrated...
Abstract The occurrence of repetitive genomic changes that provide a selective growth advantage in pluripotent stem cells is concern for their clinical application. However, the effect different culture conditions on underlying mutation rate unknown. Here we show two human embryonic cell lines derived and banked application low not substantially affected by with Rho Kinase inhibitor, commonly used routine maintenance. reduced >50% cultured under 5% oxygen, when also found alterations...
Abstract The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality. Although the vast majority hESC lines have been derived for research purposes only, about 50 established under Good Manufacturing Practice (GMP) conditions. Cell types differentiated from these designated may be used as therapy treat macular degeneration, Parkinson’s, Huntington’s, diabetes, osteoarthritis and other degenerative It essential know genetic stability...
Human pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence considerably more DNA damage during S phase cell cycle, apparently as a consequence replication stress marked by slower progression replication, activation latent origins and collapse forks. As in many cancers, which, like PSCs, shortened G1 stress, resulting may underlie higher...
Chromosome 20 abnormalities are some of the most frequent genomic changes acquired by human pluripotent stem cell (hPSC) cultures worldwide. Yet their effects on differentiation remain largely unexplored. We investigated a recurrent abnormality also found amniocentesis, isochromosome 20q (iso20q), during clinical retinal pigment epithelium differentiation. Here we show that iso20q interrupts spontaneous embryonic lineage specification. Isogenic lines revealed under conditions promote...
Abstract Background Cell therapies based on human pluripotent stem cells (hPSCs) are in clinical trials with the aim of restoring vision people age-related macular degeneration. The final cell therapy product consists retinal pigment epithelium (RPE) differentiated from hPSCs. However, hPSCs recurrently acquire genetic abnormalities that give them an advantage culture unknown effects to clinically-relevant progeny. One most common is sub-karyotype 20q11.21 copy number variant, known carry...
The enteric nervous system (ENS) is derived primarily from the vagal neural crest, a migratory multipotent cell population emerging dorsal tube between somites 1 and 7. Defects in development function of ENS cause range neuropathies, including Hirschsprung disease. Little known about signals that specify early progenitors, limiting progress generation neurons human pluripotent stem cells (hPSCs) to provide tools for disease modeling regenerative medicine neuropathies. We describe efficient...
This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information references related added subsequently workshop. Comparability is need demonstrate equivalence product after process change; recent publication states that this 'may be difficult for cell-based medicinal products'. Therefore well-managed change required which needs access good science regulatory advice developers are encouraged seek help early. The...
The final United Kingdom Regenerative Medicine Platform (UKRMP) conference held in Edinburgh's iconic McEwan Hall between 8th and November 10, 2023 saw a gathering of nearly 200 international delegates presenting exceptional science celebrating decade this initiative. UKRMP had the core mission to break down major barriers clinical translation regenerative medicine products. UKRMP2 was established as three hubs that worked closely with industry regulators: 1) Pluripotent Stem Cells...
Human embryonic stem cells (hESCs) are thought to be susceptible chromosomal rearrangements as a consequence of single cell dissociation. Compared in this study two methods dissociation that do not generate suspensions (collagenase and EDTA) with an enzymatic procedure using trypsin combined the calcium-specific chelator EGTA (TEG), does suspension, over 10 passages. Cells passaged by TEG retained normal karyotype. However, EDTA, without trypsin, acquired isochromosome p7 three replicates...
Human stem cells have the potential to transform medicine. However, hurdles remain ensure that manufacturing processes produce safe and effective products. A thorough understanding of biological occurring during manufacture is fundamental assuring these qualities thus, their acceptability regulators clinicians. Leaders in both human pluripotent somatic cells, were brought together with experts clinical translation, biomanufacturing regulation, discuss key issues appropriate conditions for...
Human embryonic stem cells (hESC) are the subject of intense investigation for use in regenerative medicine, toxicity testing, and as models study human development. Automated cell sorting will enhance isolation homogenous pools differentiated hESCs both basic studies therapeutic applications. Sorting could also be used to deplete undifferentiated, potentially tumourigenic cells. However, sensitive single disaggregation recover poorly when plated at clonal density. Here we report a method...
Abstract Although undifferentiated human embryonic stem cells (hESCs) are tumorigenic, this capacity is lost after differentiation, and hESCs being widely investigated for applications in regenerative medicine. To engineer protection against the unintentional transplantation of cells, we generated carrying a construct which α1,3-galactosyltransferase (GalT) open reading frame was transcribed from hTERT promoter (pmGT). Because endogenous GalT gene inactive, expression limited to cells. A...
Abstract Background A major challenge for the clinical use of human pluripotent stem cells is development safe, robust and controlled differentiation protocols. Adaptation research protocols using reagents designated as research-only to those which are suitable use, often referred good manufacturing practice (GMP) reagents, a crucial laborious step in translational pipeline. However, published assist this process remain very limited. Methods We adapted research-grade derivation long-term...
Establishing how to effectively manufacture cell therapies is an industry-level problem. Decentralised manufacturing of increasing importance, and its challenges are recognised by healthcare regulators with deviations comparability issues receiving specific attention from them. This paper the first report other risks encountered when implementing expansion human pluripotent stem cells (hPSCs) in automated three international site-decentralised setting. An experimental demonstrator project...
Human pluripotent stem cells (hPSCs) are a promising source of somatic for clinical applications and disease modelling. However, during culture they accumulate genetic aberrations such as amplification 20q11.21 which occurs in approximately 20% extensively cultured hPSC lines confers BCL2L1-mediated survival advantage. During the production large number required transplantation therapy these may become unavoidable has important safety implications therapies also impact upon Presently, risks...
Human pluripotent stem cells (PSC) often acquire genetic changes on prolonged culture, which pose concerns for their use in research and regenerative medicine (Amps et al., 2011, Seth 2011). The acquisition of these during culture necessarily first requires mutation then selection those mutations that provide a growth advantage. Whilst accounts the recurrent nature variants commonly reported (Draper 2004, Olariu 2010), mechanisms PSC remain largely elusive. Here we show that, contrast to...
ABSTRACT A major challenge for the clinical use of human pluripotent stem cells is development safe, robust and controlled differentiation protocols. Adaptation research protocols using reagents designated as research-only to those which are suitable use, often referred Good Manufacturing Practice (GMP) reagents, a crucial laborious step in translational pipeline. However, published assist this process remain very limited. Here we present new GMP-compliant protocol derive long-term...