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Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

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https://www.readbyqxmd.com/read/29786565/modelling-non-alcoholic-fatty-liver-disease-in-human-hepatocyte-like-cells
#1
Marcus J Lyall, Jessy Cartier, John P Thomson, Kate Cameron, Jose Meseguer-Ripolles, Eoghan O'Duibhir, Dagmara Szkolnicka, Baltasar Lucendo Villarin, Yu Wang, Giovanny Rodriguez Blanco, Warwick B Dunn, Richard R Meehan, David C Hay, Amanda J Drake
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in developed countries. An in vitro NAFLD model would permit mechanistic studies and enable high-throughput therapeutic screening. While hepatic cancer-derived cell lines are a convenient, renewable resource, their genomic, epigenomic and functional alterations mean their utility in NAFLD modelling is unclear. Additionally, the epigenetic mark 5-hydroxymethylcytosine (5hmC), a cell lineage identifier, is rapidly lost during cell culture, alongside expression of the Ten-eleven-translocation ( TET ) methylcytosine dioxygenase enzymes, restricting meaningful epigenetic analysis...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786564/developing-defined-substrates-for-stem-cell-culture-and-differentiation
#2
REVIEW
Louise Hagbard, Katherine Cameron, Paul August, Christopher Penton, Malin Parmar, David C Hay, Therése Kallur
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 in vitro , but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786563/cell-based-liver-therapies-past-present-and-future
#3
REVIEW
Valeria Iansante, Anil Chandrashekran, Anil Dhawan
Liver transplantation represents the standard treatment for people with an end-stage liver disease and some liver-based metabolic disorders; however, shortage of liver donor tissues limits its availability. Furthermore, whole liver replacement eliminates the possibility of using native liver as a possible target for future gene therapy in case of liver-based metabolic defects. Cell therapy has emerged as a potential alternative, as cells can provide the hepatic functions and engraft in the liver parenchyma...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786562/application-of-hepatocyte-like-cells-to-enhance-hepatic-safety-risk-assessment-in-drug-discovery
#4
REVIEW
Dominic P Williams
Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786561/impedance-based-cellular-assays-for-regenerative-medicine
#5
REVIEW
W Gamal, H Wu, I Underwood, J Jia, S Smith, P O Bagnaninchi
Therapies based on regenerative techniques have the potential to radically improve healthcare in the coming years. As a result, there is an emerging need for non-destructive and label-free technologies to assess the quality of engineered tissues and cell-based products prior to their use in the clinic. In parallel, the emerging regenerative medicine industry that aims to produce stem cells and their progeny on a large scale will benefit from moving away from existing destructive biochemical assays towards data-driven automation and control at the industrial scale...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786560/microfabrication-of-liver-and-heart-tissues-for-drug-development
#6
REVIEW
Grace E Brown, Salman R Khetani
Drug-induced liver- and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black-box warnings on marketed drugs. Unfortunately, animal testing has proven to be insufficient for accurately predicting drug-induced liver- and cardiotoxicity across many drug classes, likely due to significant differences in tissue functions across species. Thus, the field of in vitro human tissue engineering has gained increasing importance over the last 10 years...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786559/three-dimensional-bioprinting-of-stem-cell-derived-tissues-for-human-regenerative-medicine
#7
REVIEW
Gregor Skeldon, Baltasar Lucendo-Villarin, Wenmiao Shu
Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786558/new-substrates-for-stem-cell-control
#8
REVIEW
Sara Schmidt, Annamaria Lilienkampf, Mark Bradley
The capacity to culture stem cells in a controllable, robust and scalable manner is necessary in order to develop successful strategies for the generation of cellular and tissue platforms for drug screening, toxicity testing, tissue engineering and regenerative medicine. Creating substrates that support the expansion, maintenance or directional differentiation of stem cells would greatly aid these efforts. Optimally, the substrates used should be chemically defined and synthetically scalable, allowing growth under defined, serum-free culture conditions...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786557/the-gene-regulatory-network-of-mesc-differentiation-a-benchmark-for-reverse-engineering-methods
#9
Johannes Meisig, Nils Blüthgen
A large body of data have accumulated that characterize the gene regulatory network of stem cells. Yet, a comprehensive and integrative understanding of this complex network is lacking. Network reverse engineering methods that use transcriptome data to derive these networks may help to uncover the topology in an unbiased way. Many methods exist that use co-expression to reconstruct networks. However, it remains unclear how these methods perform in the context of stem cell differentiation, as most systematic assessments have been made for regulatory networks of unicellular organisms...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786556/assessment-of-stem-cell-differentiation-based-on-genome-wide-expression-profiles
#10
REVIEW
Patricio Godoy, Wolfgang Schmidt-Heck, Birte Hellwig, Patrick Nell, David Feuerborn, Jörg Rahnenführer, Kathrin Kattler, Jörn Walter, Nils Blüthgen, Jan G Hengstler
In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell-derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived 'mature' cells and primary target cells or tissue...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786555/innate-immunity-in-stem-cell-derived-hepatocytes
#11
REVIEW
Lena Fischer, David C Hay, Cliona O'Farrelly
Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786554/a-human-ipsc-line-capable-of-differentiating-into-functional-macrophages-expressing-zsgreen-a-tool-for-the-study-and-in-vivo-tracking-of-therapeutic-cells
#12
Martha Lopez-Yrigoyen, Antonella Fidanza, Luca Cassetta, Richard A Axton, A Helen Taylor, Jose Meseguer-Ripolles, Anestis Tsakiridis, Valerie Wilson, David C Hay, Jeffrey W Pollard, Lesley M Forrester
We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786553/from-skeletal-development-to-the-creation-of-pluripotent-stem-cell-derived-bone-forming-progenitors
#13
REVIEW
Wai Long Tam, Frank P Luyten, Scott J Roberts
Bone has many functions. It is responsible for protecting the underlying soft organs, it allows locomotion, houses the bone marrow and stores minerals such as calcium and phosphate. Upon damage, bone tissue can efficiently repair itself. However, healing is hampered if the defect exceeds a critical size and/or is in compromised conditions. The isolation or generation of bone-forming progenitors has applicability to skeletal repair and may be used in tissue engineering approaches. Traditionally, bone engineering uses osteochondrogenic stem cells, which are combined with scaffold materials and growth factors...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786552/intestinal-organoids-for-modelling-intestinal-development-and-disease
#14
REVIEW
Kathryn L Fair, Jennifer Colquhoun, Nicholas R F Hannan
Gastrointestinal diseases are becoming increasingly prevalent in developed countries. Immortalized cells and animal models have delivered important but limited insight into the mechanisms that initiate and propagate these diseases. Human-specific models of intestinal development and disease are desperately needed that can recapitulate structure and function of the gut in vitro Advances in pluripotent stem cells and primary tissue culture techniques have made it possible to culture intestinal epithelial cells in three dimensions that self-assemble to form 'intestinal organoids'...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786551/three-dimensional-cell-culture-from-evolution-to-revolution
#15
REVIEW
Sharmin Alhaque, Michael Themis, Hassan Rashidi
Recent advances in the isolation of tissue-resident adult stem cells and the identification of inductive factors that efficiently direct differentiation of human pluripotent stem cells along specific lineages have facilitated the development of high-fidelity modelling of several tissues in vitro Many of the novel approaches have employed self-organizing three-dimensional (3D) culturing of organoids, which offer several advantages over conventional two-dimensional platforms. Organoid technologies hold great promise for modelling diseases and predicting the outcome of drug responses in vitro Here, we outline the historical background and some of the recent advances in the field of three-dimensional organoids...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786550/generation-of-defined-neural-populations-from-pluripotent-stem-cells
#16
REVIEW
Sarah F McComish, Maeve A Caldwell
Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS)...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786549/pluripotent-stem-cells-induction-and-self-renewal
#17
REVIEW
R Abu-Dawud, N Graffmann, S Ferber, W Wruck, J Adjaye
Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewal in vitro and their ability to differentiate into cell types representative of the three embryonic germ layers-mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786548/designer-human-tissue-coming-to-a-lab-near-you
#18
David C Hay, Cliona O'Farrelly
Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology 'in a dish' or immune-matched cell-based therapies for the clinic...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29735744/correction-to-migration-in-the-anthropocene-how-collective-navigation-environmental-system-and-taxonomy-shape-the-vulnerability-of-migratory-species
#19
Molly Hardesty-Moore, Stefanie Deinet, Robin Freeman, Georgia C Titcomb, Erin M Dillon, Keenan Stears, Maggie Klope, An Bui, Devyn Orr, Hillary S Young, Ana Miller-Ter Kuile, Lacey F Hughey, Douglas J McCauley
No abstract text is available yet for this article.
June 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29735743/the-substrate-specificity-of-eukaryotic-cytosolic-chaperonin-cct
#20
REVIEW
Keith R Willison
The cytosolic chaperonin CCT (chaperonin containing TCP-1) is an ATP-dependent double-ring protein machine mediating the folding of members of the eukaryotic cytoskeletal protein families. The actins and tubulins are obligate substrates of CCT because they are completely dependent on CCT activity to reach their native states. Genetic and proteomic analysis of the CCT interactome in the yeast Saccharomyces cerevisiae revealed a CCT network of approximately 300 genes and proteins involved in many fundamental biological processes...
June 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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