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Dive into the research topics where Ian S. Currie is active.

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Featured researches published by Ian S. Currie.


Proceedings of the National Academy of Sciences of the United States of America | 2008

Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling

David C. Hay; Judy Fletcher; Catherine Payne; John D. Terrace; Ronald C.J. Gallagher; Jan Snoeys; James R. Black; Davina Wojtacha; Kay Samuel; Zara Hannoun; Anne Pryde; Celine Filippi; Ian S. Currie; Stuart J. Forbes; James A. Ross; Philip N. Newsome; John P. Iredale

Human embryonic stem cells (hESCs) are a valuable source of pluripotential primary cells. To date, however, their homogeneous cellular differentiation to specific cell types in vitro has proven difficult. Wnt signaling has been shown to play important roles in coordinating development, and we demonstrate that Wnt3a is differentially expressed at critical stages of human liver development in vivo. The essential role of Wnt3a in hepatocyte differentiation from hESCs is paralleled by our in vitro model, demonstrating the importance of a physiologic approach to cellular differentiation. Our studies provide compelling evidence that Wnt3a signaling is important for coordinated hepatocellular function in vitro and in vivo. In addition, we demonstrate that Wnt3a facilitates clonal plating of hESCs exhibiting functional hepatic differentiation. These studies represent an important step toward the use of hESC-derived hepatocytes in high-throughput metabolic analysis of human liver function.


BioMed Research International | 2010

Liver Development, Regeneration, and Carcinogenesis

Janet Kung; Ian S. Currie; Stuart J. Forbes; James A. Ross

The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.


Cloning and Stem Cells | 2008

The Inhibitory Role of Stromal Cell Mesenchyme on Human Embryonic Stem Cell Hepatocyte Differentiation is Overcome by Wnt3a Treatment

Judy Fletcher; Wei Cui; Kay Samuel; James R. Black; Zara Hannoun; Ian S. Currie; John D. Terrace; Catherine Payne; Celine Filippi; Philip N. Newsome; Stuart J. Forbes; James A. Ross; John P. Iredale; David C. Hay

Pluripotent stem cells are derived from the inner cell mass of preimplantation embryos, and display the ability of the embryonic founder cells by forming all three germ lineages in vitro. It is well established that the cellular niche plays an important role in stem cell maintenance and differentiation. Stem cells generally have limited function without the specialized microenvironment of the niche that provides key cell-cell contact, soluble mediators, and extracellular matrices. We were interested in the role that Wnt signaling, in particular Wnt3a, played in human embryonic stem cell (hESC) differentiation to hepatic endoderm in vitro. hESC differentiation to hepatic endoderm was efficient in pure stem cell populations. However, in younger hESC lines, generating stromal cell mesenchyme, our model was very inefficient. The negative effect of stroma could be reversed by pretreating hESCs with Wnt3a prior to the onset of hepatocyte differentiation. Wnt3a pretreatment reinstated efficient hESC differentiation to hepatic endoderm. These studies represent an important step in understanding hepatocyte differentiation from hESCs and the role played by the cellular niche in vitro.


Experimental Cell Research | 2009

Side population cells in developing human liver are primarily haematopoietic progenitor cells

John D. Terrace; David C. Hay; Kay Samuel; Catherine Payne; Richard A. Anderson; Ian S. Currie; Rowan W. Parks; Stuart J. Forbes; James A. Ross

Side population (SP) cells have recently been identified in a number of tissues although their phenotype and functional abilities are poorly understood. Surface marker characterisation and functional assessment of developing liver SP cells might allow for their isolation and manipulation using clinically relevant techniques. It was hypothesised that SP cells are present early during human liver development and contribute to haematopoietic and epithelial lineage generation. Whilst the SP population remained positive for CD34 during the 1st and 2nd trimester, 1st trimester SP cells were more highly enriched for haematopoietic and epithelial progenitor activity than those from the 2nd trimester in vitro. Marker expression and functional similarities indicate that SP cells in developing human liver may share a temporal relationship with oval/progenitor cells, responsible for liver regeneration after massive or chronic hepatic injury. Furthermore, modification of SP integrin expression during development suggests a potential adaptive interaction with niche components such as fibronectin. Improved understanding of developing human liver SP cells will contribute to the generation of novel cell-based therapies for liver disease.


Experimental Cell Research | 2010

Portal venous endothelium in developing human liver contains haematopoietic and epithelial progenitor cells

John D. Terrace; David C. Hay; Kay Samuel; Richard A. Anderson; Ian S. Currie; Rowan W. Parks; Stuart J. Forbes; James A. Ross

Future treatments for chronic liver disease are likely to involve manipulation of liver progenitor cells (LPCs). In the human, data characterising the regenerative response is limited and the origin of adult LPCs is unknown. However, these remain critical factors in the design of cell-based liver therapies. The developing human liver provides an ideal model to study cell lineage derivation from progenitors and to understand how foetal haematopoiesis and liver development might explain the nature of the adult LPC population. In 1st trimester human liver, portal venous endothelium (PVE) expressed adult LPC markers and markers of haematopoietic progenitor cells (HPCs) shared with haemogenic endothelium found in the embryonic dorsal aorta. Sorted PVE cells were able to generate hepatoblast-like cells co-expressing CK18 and CK19 in addition to Dlk/pref-1, E-cadherin, albumin and fibrinogen in vitro. Furthermore, PVE cells could initiate haematopoiesis. These data suggest that PVE shares phenotypical and functional similarities both with adult LPCs and embryonic haemogenic endothelium. This indicates that a temporal relationship might exist between progenitor cells in foetal liver development and adult liver regeneration, which may involve progeny of PVE.


Transplantation | 2018

Better Graft Survival with no Ischemic Cholangiopathy in DCD Liver Transplantation in the UK using Normothermic Regional Perfusion (NRP)

Gabriel C. Oniscu; Andrew J. Butler; Fiona Hunt; Stephen R. Large; Andrew Sutherland; S. Messer; Ian S. Currie; Sarah Upon; John D. Terrace; Chris Watson

Background Normothermic regional perfusion, whereby the donor is placed on an extracorporeal circuit to circulate oxygenated blood to the abdominal viscera after death, is increasingly being used in controlled donation after circulatory death (DCD) donation. We evaluated the joint experience of the two centres pioneering this technique in the UK and compared NRP DCD liver transplants to non-NRP DCD livers transplanted at each centre in the same period. Methods Between 1/1/2011 and 31/5/17, 44 patients underwent liver transplantation following NRP; these were compared to 185 DCD liver transplants without NRP performed in the same period. NRP was performed for a median 123 (IQR 101-130) minutes before in-situ cold perfusion. Results Table 1 summarises the results. There was no significant difference in the recipient age (58 vs 61) or UK End Stage Liver disease (UKELD) score (55.7 NRP vs 54.3 non-NRP) between groups. 90 day patient survival was similar (100% NRP vs 96.7% non-NRP). There was a significant reduction in ischemic cholangiopathy and early allograft dysfunction with a better graft survival at 90 days. Conclusion Livers from DCD donors undergoing NRP have a lower incidence of primary non function and early allograft dysfunction, fewer biliary complications, and significantly better early graft survival. Table. No title available.


American Journal of Physiology-gastrointestinal and Liver Physiology | 2006

Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1

Neil M. Masson; Ian S. Currie; John D. Terrace; O. James Garden; Rowan W. Parks; James A. Ross


Stem Cells and Development | 2007

Progenitor cell characterization and location in the developing human liver

John D. Terrace; Ian S. Currie; David C. Hay; Neil M. Masson; Richard A. Anderson; Stuart J. Forbes; Rowan W. Parks; James A. Ross


European Society for Organ Transplantation | 2017

Human performance assessment of multi-organ retrieval with the joint scrub practitioner in the United Kingdom

Amanda Martindale; Hugh Richards; Galina Morozova; John Stirling; Ian S. Currie


British Transplant Society Congress | 2017

Human performance assessment of multi-organ retrieval with the joint scrub practitioner

Amanda Martindale; Hugh Richards; Galina Morozova; John Stirling; Ian S. Currie

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David C. Hay

University of Edinburgh

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Kay Samuel

University of Edinburgh

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