All Outputs (61)

Surface Plasmon Resonance Imaging of Excitable Cells (2018)
Preprint / Working Paper
Howe, C. L., Webb, K. F., Abayzeed, S. A., Anderson, D. J., Denning, C., & Russell, N. A. Surface Plasmon Resonance Imaging of Excitable Cells

Surface plasmons are highly sensitive to refractive index variations adjacent to the surface. This sensitivity has been exploited successfully for chemical and biological assays. In these systems, a surface plasmon resonance (SPR)-based sensor detect... Read More about Surface Plasmon Resonance Imaging of Excitable Cells.

CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy (2018)
Journal Article
Mosqueira, D., Mannhardt, I., Bhagwan, J. R., Lis-Slimak, K., Katili, P., Scott, E., Hassan, M., Prondzynski, M., Harmer, S. C., Tinker, A., Smith, J. G., Carrier, L., Williams, P. M., Gaffney, D., Eschenhagen, T., Hansen, A., & Denning, C. (2018). CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy. European Heart Journal, 39(43), 3879-3892. https://doi.org/10.1093/eurheartj/ehy249

Aims: Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening and heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardi... Read More about CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy.

Simplified footprint-free Cas9/CRISPR editing of cardiac-associated genes in human pluripotent stem cells (2018)
Journal Article
Kondrashov, A., Hoang, M. D., Smith, J. G., Bhagwan, J. R., Duncan, G., Mosqueira, D., Barbadillo Munoz, M., Vo, N. T., & Denning, C. (in press). Simplified footprint-free Cas9/CRISPR editing of cardiac-associated genes in human pluripotent stem cells. Stem Cells and Development, 27(6), https://doi.org/10.1089/scd.2017.0268

Modelling disease with hPSCs is hindered because the impact on cell phenotype from genetic variability between individuals can be greater than from the pathogenic mutation. While ‘footprint-free’ Cas9/CRISPR editing solves this issue, existing approa... Read More about Simplified footprint-free Cas9/CRISPR editing of cardiac-associated genes in human pluripotent stem cells.

MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo (2017)
Journal Article
Sala, L., van Meer, B., Tertoolen, L., Bakkers, J., Bellin, M., Davis, R., …Burton, F. (2018). MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo. Circulation Research, 122(3), e5. https://doi.org/10.1161/CIRCRESAHA.117.312067

Rationale: There are several methods to measure cardiomyocyte (CM) and muscle contraction but these require customized hardware, expensive apparatus and advanced informatics or can only be used in single experimental models. Consequently, data and te... Read More about MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo.

Drug-mediated shortening of action potentials in LQTS2 hiPSC-cardiomyocytes (2017)
Journal Article
Duncan, G., Firth, K. S., George, V., Hoang, M. D., Staniforth, A., Smith, G., & Denning, C. (2017). Drug-mediated shortening of action potentials in LQTS2 hiPSC-cardiomyocytes. Stem Cells and Development, 26(23), https://doi.org/10.1089/scd.2017.0172

Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are now a well-established modality for modeling genetic disorders of the heart. This is especially so for long QT syndrome (LQTS), which is caused by perturbation of ion... Read More about Drug-mediated shortening of action potentials in LQTS2 hiPSC-cardiomyocytes.

Dynamics of 5-carboxylcytosine during hepatic differentiation: potential general role for active demethylation by DNA repair in lineage specification (2017)
Journal Article
Lewis, L. C., Lo, P. C. K., Foster, J. M., Dai, N., Correa, I. R., Durczak, P. M., …Ruzov, A. (in press). Dynamics of 5-carboxylcytosine during hepatic differentiation: potential general role for active demethylation by DNA repair in lineage specification. Epigenetics, 12(4), https://doi.org/10.1080/15592294.2017.1292189

Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-c... Read More about Dynamics of 5-carboxylcytosine during hepatic differentiation: potential general role for active demethylation by DNA repair in lineage specification.

Can human pluripotent stem cell-derived cardiomyocytes advance understanding of muscular dystrophies? (2016)
Journal Article
Kalra, S., Montanaro, F., & Denning, C. (2016). Can human pluripotent stem cell-derived cardiomyocytes advance understanding of muscular dystrophies?. Journal of Neuromuscular Diseases, 3(3), 309-332. https://doi.org/10.3233/JND-150133

Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mo... Read More about Can human pluripotent stem cell-derived cardiomyocytes advance understanding of muscular dystrophies?.

Identification of polymer surface adsorbed proteins implicated in pluripotent human embryonic stem cell expansion (2016)
Journal Article
Hammad, M., Rao, W., Smith, J. G. W., Anderson, D. G., Langer, R., Young, L. E., …Alexander, M. R. (2016). Identification of polymer surface adsorbed proteins implicated in pluripotent human embryonic stem cell expansion. Biomaterials Science, 4(9), 1381-1391. https://doi.org/10.1039/c6bm00214e

Improved biomaterials are required for application in regenerative medicine, biosensing, and as medical devices. The response of cells to the chemistry of polymers cultured in media is generally regarded as being dominated by proteins adsorbed to the... Read More about Identification of polymer surface adsorbed proteins implicated in pluripotent human embryonic stem cell expansion.

Automated electrophysiological and pharmacological evaluation of human pluripotent stem cell-derived cardiomyocytes (2016)
Journal Article
Rajamohan, D., Kalra, S., Hoang, M. D., George, V., Staniforth, A., Russell, H., …Denning, C. (2016). Automated electrophysiological and pharmacological evaluation of human pluripotent stem cell-derived cardiomyocytes. Stem Cells and Development, 25(6), https://doi.org/10.1089/scd.2015.0253

Automated planar patch clamp systems are widely used in drug evaluation studies because of their ability to provide accurate, reliable, and reproducible data in a high-throughput manner. Typically, CHO and HEK tumorigenic cell lines overexpressing si... Read More about Automated electrophysiological and pharmacological evaluation of human pluripotent stem cell-derived cardiomyocytes.

High throughput screening for discovery of materials that control stem cell fate (2016)
Journal Article
Patel, A. K., Tibbitt, M., Celiz, A. D., Davies, M. C., Langer, R., Denning, C., …Anderson, D. G. (2016). High throughput screening for discovery of materials that control stem cell fate. Current Opinion in Solid State and Materials Science, 20(4), 202-211. https://doi.org/10.1016/j.cossms.2016.02.002

Insights into the complex stem cell niche have identified the cell–material interface to be a potent regulator of stem cell fate via material properties such as chemistry, topography and stiffness. In light of this, materials scientists have the oppo... Read More about High throughput screening for discovery of materials that control stem cell fate.

Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides (2016)
Journal Article
Dixon, J. E., Osman, G., Morris, G. E., Markides, H., Rotherham, M., Bayoussef, Z., …Shakesheff, K. M. (2016). Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides. Proceedings of the National Academy of Sciences, 113(3), E291-E299. https://doi.org/10.1073/pnas.1518634113

Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets.... Read More about Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides.

Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform (2015)
Journal Article
Denning, C., Borgdorff, V., Crutchley, J., Firth, K. S., George, V., Kalra, S., …Young, L. E. (2016). Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform. BBA - Biochimica et Biophysica Acta, 1863(7), https://doi.org/10.1016/j.bbamcr.2015.10.014

Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas... Read More about Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform.

A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays (2015)
Journal Article
Patel, A. K., Celiz, A. D., Rajamohan, D., Anderson, D. G., Langer, R., Davies, M. C., …Denning, C. (2015). A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays. Biomaterials, 61, https://doi.org/10.1016/j.biomaterials.2015.05.019

Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components suc... Read More about A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays.

Discovery of a Novel Polymer for Human Pluripotent Stem Cell Expansion and Multilineage Differentiation (2015)
Journal Article
Smith, J. G. W., Celiz, A. D., Smith, J. G., Patel, A. K., Hook, A. L., Rajamohan, D., …Alexander, M. R. (2015). Discovery of a Novel Polymer for Human Pluripotent Stem Cell Expansion and Multilineage Differentiation. Advanced Materials, 27(27), 4006-4012. https://doi.org/10.1002/adma.201501351

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. A scalable and cost-effective synthetic polymer substrate that supports robust expansion and subsequent multilineage differentiation of human pluripotent stem cells (hPSCs) with defined commercial... Read More about Discovery of a Novel Polymer for Human Pluripotent Stem Cell Expansion and Multilineage Differentiation.

Applications of Raman micro-spectroscopy to stem cell technology: label-free molecular discrimination and monitoring cell differentiation. (2015)
Journal Article
Ghita, A., Pascut, F. C., Sottile, V., Denning, C., & Notingher, I. (2015). Applications of Raman micro-spectroscopy to stem cell technology: label-free molecular discrimination and monitoring cell differentiation. EPJ Techniques and Instrumentation, 2, Article 6. https://doi.org/10.1140/epjti/s40485-015-0016-8

Stem cell therapy is widely acknowledged as a key medical technology of the 21st century which may provide treatments for many currently incurable diseases. These cells have an enormous potential for cell replacement therapies to cure diseases such a... Read More about Applications of Raman micro-spectroscopy to stem cell technology: label-free molecular discrimination and monitoring cell differentiation..

Materials for stem cell factories of the future (2014)
Journal Article
Celiz, A. D., Smith, J. G., Langer, R., Anderson, D. G., Barrett, D. A., Winkler, D. A., …Alexander, M. R. (2014). Materials for stem cell factories of the future. Nature Materials, 13(6), 570-579. https://doi.org/10.1038/nmat3972

The materials community is now identifying polymeric substrates that could permit translation of human pluripotent stem cells (hPSCs) from lab-based research to industrial scale biomedicine. Well defined materials are required to allow cell banking a... Read More about Materials for stem cell factories of the future.

Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation (2014)
Journal Article
Dixon, J. E., Shah, D. A., Rogers, C., Hall, S., Weston, N., Parmenter, C. D., …Shakesheff, K. M. (2014). Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation. Proceedings of the National Academy of Sciences, 111(15), 5580-5585. https://doi.org/10.1073/pnas.1319685111

The ability of materials to define the architecture and microenvironment experienced by cells provides new opportunities to direct the fate of human pluripotent stem cells (HPSCs) [Robinton DA, Daley GQ (2012) Nature 481(7381):295-305]. However, the... Read More about Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation.

Exon skipping and gene transfer restore dystrophin expression in human induced pluripotent stem cells-cardiomyocytes harboring DMD mutations (2013)
Journal Article
Dick, E., Kalra, S., Anderson, D., George, V., Ritso, M., Laval, S. H., …Denning, C. (2013). Exon skipping and gene transfer restore dystrophin expression in human induced pluripotent stem cells-cardiomyocytes harboring DMD mutations. Stem Cells and Development, 22(20), https://doi.org/10.1089/scd.2013.0135

With an incidence of 1:3,500 to 5,000 in male children, Duchenne muscular dystrophy (DMD) is an X-linked disorder in which progressive muscle degeneration occurs and affected boys usually die in their twenties or thirties. Cardiac involvement occurs... Read More about Exon skipping and gene transfer restore dystrophin expression in human induced pluripotent stem cells-cardiomyocytes harboring DMD mutations.

Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes (2013)
Journal Article
Matsa, E., Dixon, J. E., Medway, C., Georgiou, O., Patel, M. J., Morgan, K., …Denning, C. (2014). Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes. European Heart Journal, 35(16), 1078-1087. https://doi.org/10.1093/eurheartj/eht067

Aims Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs... Read More about Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes.

Current status of drug screening and disease modelling in human pluripotent stem cells (2013)
Journal Article
Rajamohan, D., Matsa, E., Kalra, S., Crutchley, J., Patel, A., George, V., & Denning, C. (2013). Current status of drug screening and disease modelling in human pluripotent stem cells. BioEssays, 35(3), https://doi.org/10.1002/bies.201200053

The emphasis in human pluripotent stem cell (hPSC) technologies has shifted from cell therapy to in vitro disease modelling and drug screening. This review examines why this shift has occurred, and how current technological limitations might be overc... Read More about Current status of drug screening and disease modelling in human pluripotent stem cells.