المؤلفون: Ruiz Puig, Carlos

المساهمون: Lu, Xin, Rittscher, Jens

مصطلحات موضوعية: 616.99, Esophagus, Three-dimensional printing, Medicine, Cancer

الوصف: Oesophageal adenocarcinoma originates in the gastroesophageal junction and has a poor prognosis. Barrett's oesophagus is a common, innocuous condition occurring prior to most adenocarcinoma cases. This lesion is frequent in patients suffering from gastroduodenal reflux and involves columnar cells replacing a segment of the squamous lining of the distal oesophagus. High variability in the length of the segment exists between individuals and typically patients with longer lesions have an increased risk of developing adenocarcinoma. However, the pathways promoting this replacement and determining its final length are unknown. In this thesis, I investigate models to study this phenomenon in vitro. In the first part of this thesis, I describe a system that I developed to study interactions between epithelial cell populations and apply it to combinations of cells which are crucial for Barrett's oesophagus progression. My findings indicate that squamous and early Barrett's oesophagus derived cells form stable junctions and that reflux-like epidermal growth factor concentrations can disrupt this stability. In part two, I adapt existing 3D culture methods to study heterotypic junctions in vitro. Combining oil bath and plastic printing techniques, I have constructed rings with organoid epithelial lining. I demonstrate as well that it is possible to control the ring's size via the addition of fibroblasts into the collagen. Through addition of a divider, I was able to recapitulate heterotypic junctions between organoid populations and, by making the moulds higher, I show that it is possible to generate tube structures using the same technique. Additionally, I demonstrate that using fibroblast gradients in the tubes can control their shape. Building upon the contractibility of the fibroblasts, I also show that adaptors can be fixed at the ends of the tubes to control flow through it. Using this system, I am able to coat the tube's lumen with epithelia and infect the cells with pathogens to recapitulate a more natural infection. Lastly, I generated an endoscopic mucosal resection biobank for microdissection with the samples being annotated with the assistance of pathologists. I then validated this system by micro-dissecting three candidate patients.

الوصول الحر: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.830416Test

المؤلفون: Buti, Ludovico, Ruiz-Puig, Carlos, Sangberg, Dennis, Leissing, Thomas M., Brewer, R. Camille, Owen, Richard P., Sgromo, Bruno, Royer, Christophe, Ebner, Daniel, Lu, Xin

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2020 Feb 01. 117(5), 2645-2655.

الوصول الحر: https://www.jstor.org/stable/26928865Test

المؤلفون: Zhou, Linna, Ruiz‐Puig, Carlos, Jacobs, Brittany‐Amber, Han, Xiaoyue, Lisle, Richard, Bayley, Hagan, Lu, Xin

المصدر: Advanced Functional Materials ; volume 31, issue 6 ; ISSN 1616-301X 1616-3028

الإتاحة: https://doi.org/10.1002/adfm.202170036Test

المؤلفون: Zhou, Linna, Ruiz‐Puig, Carlos, Jacobs, Brittany‐Amber, Han, Xiaoyue, Lisle, Richard, Bayley, Hagan, Lu, Xin

المساهمون: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, European Research Council, Ludwig Institute for Cancer Research

المصدر: Advanced Functional Materials ; volume 31, issue 6 ; ISSN 1616-301X 1616-3028

الوصف: Bioengineered gastrointestinal (GI) tracts have potential applications in regenerative medicine and disease modeling. Methods for engineering tubular GI tracts containing natural extracellular matrix (ECM) are currently limited. Here, the fabrication of collagen tubes with designed shapes by using lipid bilayer supported droplet networks is reported. Droplets containing cells and collagen are arrayed in lipid‐containing oil to form droplet networks, which undergo thermal gelation to provide continuous collagen tubes. A variety of tubular GI tissues are fabricated. For example, human intestinal organoids embedded in the collagen tubes migrate to the luminal surfaces and fuse to form a continuous epithelial layer, mimicking aspects of intestinal tissue structure. Fibroblasts embedded in the collagen induce a cell density dependent contraction of the tubes. Complex tubular structures are produced by patterning droplets containing different densities of fibroblasts. The fibroblast‐containing collagen tubes are seeded with various epithelial cells at their luminal surfaces to form gastric and colonic tissues, which comprise monolayers or multilayers of epithelial cells and fibroblast‐containing subepithelial layers. The engineered gastric tissues are susceptible to infection with Helicobacter pylori . The versatile technique allows the construction of tubular GI tracts containing ECM and layered structures, with broad potential applications in disease research and regenerative medicine.

الإتاحة: https://doi.org/10.1002/adfm.202007514Test

المؤلفون: Zhou, Felix Y, Ruiz-Puig, Carlos, Owen, Richard P, White, Michael J, Rittscher, Jens, Lu, Xin

المساهمون: Ludwig Institute for Cancer Research, Engineering and Physical Sciences Research Council, Oxford Health Services Research Committee, Oxford University Clinical Academic Graduate School, Cancer Research UK

المصدر: eLife ; volume 8 ; ISSN 2050-084X

الوصف: Correct cell/cell interactions and motion dynamics are fundamental in tissue homeostasis, and defects in these cellular processes cause diseases. Therefore, there is strong interest in identifying factors, including drug candidates that affect cell/cell interactions and motion dynamics. However, existing quantitative tools for systematically interrogating complex motion phenotypes in timelapse datasets are limited. We present Motion Sensing Superpixels (MOSES), a computational framework that measures and characterises biological motion with a unique superpixel ‘mesh’ formulation. Using published datasets, MOSES demonstrates single-cell tracking capability and more advanced population quantification than Particle Image Velocimetry approaches. From > 190 co-culture videos, MOSES motion-mapped the interactions between human esophageal squamous epithelial and columnar cells mimicking the esophageal squamous-columnar junction, a site where Barrett’s esophagus and esophageal adenocarcinoma often arise clinically. MOSES is a powerful tool that will facilitate unbiased, systematic analysis of cellular dynamics from high-content time-lapse imaging screens with little prior knowledge and few assumptions.

الإتاحة: https://doi.org/10.7554/elife.40162Test
https://cdn.elifesciences.org/articles/40162/elife-40162-v2.pdfTest
https://cdn.elifesciences.org/articles/40162/elife-40162-v2.xmlTest
https://elifesciences.org/articles/40162Test

المؤلفون: Zhou, Felix Yuran, Ruiz-Puig, Carlos, Owen, Richard P, White, Michael J, Rittscher, Jens, Lu, Xin

المصدر: eLife ; volume 8 ; ISSN 2050-084X

مصطلحات موضوعية: General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience

الإتاحة: https://doi.org/10.7554/elife.49823Test
https://cdn.elifesciences.org/articles/49823/elife-49823-v1.xmlTest
https://elifesciences.org/articles/49823Test

المؤلفون: Owen, Richard Peter, White, Michael Joseph, Severson, David Tyler, Braden, Barbara, Bailey, Adam, Goldin, Robert, Wang, Lai Mun, Ruiz-Puig, Carlos, Maynard, Nicholas David, Green, Angie, Piazza, Paolo, Buck, David, Middleton, Mark Ross, Ponting, Chris Paul, Schuster-Böckler, Benjamin, Lu, Xin

المصدر: Nature Communications ; volume 9, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett’s oesophagus, marked by LEFTY1 and OLFM4 , exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice.

الإتاحة: https://doi.org/10.1038/s41467-018-06796-9Test
https://www.nature.com/articles/s41467-018-06796-9.pdfTest
https://www.nature.com/articles/s41467-018-06796-9Test

المؤلفون: Zhou, Linna^1,2 (AUTHOR), Ruiz‐Puig, Carlos¹ (AUTHOR), Jacobs, Brittany‐Amber¹ (AUTHOR), Han, Xiaoyue¹ (AUTHOR), Lisle, Richard¹ (AUTHOR), Bayley, Hagan² (AUTHOR) hagan.bayley@chem.ox.ac.uk, Lu, Xin¹ (AUTHOR) xin.lu@ludwig.ox.ac.uk

المصدر: Advanced Functional Materials. 2/3/2021, Vol. 31 Issue 6, p1-10. 10p.

مصطلحات موضوعية: *HELICOBACTER pylori infections, *COLLAGEN, *GASTRIC mucosa, *GASTROINTESTINAL system, *EXTRACELLULAR matrix, *REGENERATIVE medicine, *PARIETAL cells

مستخلص: Bioengineered gastrointestinal (GI) tracts have potential applications in regenerative medicine and disease modeling. Methods for engineering tubular GI tracts containing natural extracellular matrix (ECM) are currently limited. Here, the fabrication of collagen tubes with designed shapes by using lipid bilayer supported droplet networks is reported. Droplets containing cells and collagen are arrayed in lipid‐containing oil to form droplet networks, which undergo thermal gelation to provide continuous collagen tubes. A variety of tubular GI tissues are fabricated. For example, human intestinal organoids embedded in the collagen tubes migrate to the luminal surfaces and fuse to form a continuous epithelial layer, mimicking aspects of intestinal tissue structure. Fibroblasts embedded in the collagen induce a cell density dependent contraction of the tubes. Complex tubular structures are produced by patterning droplets containing different densities of fibroblasts. The fibroblast‐containing collagen tubes are seeded with various epithelial cells at their luminal surfaces to form gastric and colonic tissues, which comprise monolayers or multilayers of epithelial cells and fibroblast‐containing subepithelial layers. The engineered gastric tissues are susceptible to infection with Helicobacter pylori. The versatile technique allows the construction of tubular GI tracts containing ECM and layered structures, with broad potential applications in disease research and regenerative medicine. [ABSTRACT FROM AUTHOR]

المؤلفون: Zhou, Felix Y, Ruiz-Puig, Carlos, Owen, Richard P, White, Michael J, Rittscher, Jens, Lu, Xin

الإتاحة: https://doi.org/10.7554/elife.40162.048Test