Cardiovascular disease (CVD) comprehensively describes a range of pathologies of the heart and/or blood vessels. These disorders differ markedly in time-scale of development, and relative contributory effects of genes and environment. Largely due to this breadth, and their causes and effects, the range of investigation, assessment, and treatment strategies available is large. The diversity of the diseases, disease processes, and genetic differences between individuals could obscure disease associations in terms of the proteomic signatures of each disorder. Thus, a panel of independent disease-related proteins considered together should be less prone to this noise and help provide much more robust analysis and indication of disease. The publication featured below and the reagents (multi-plex immunoassays or single target ELISA and antibodies) mentioned in this post may contribute in helping you to identify such diseases signature. [Read more…]
Kupffer cells in co-culture models for liver inflammation studies
Kupffer primary cells are macrophages endogenous to the liver which have the ability to modulate hepatic inflammation and injury associated with various pathophysiologies and toxicities. Pro-inflammatory cytokines released by activated Kupffer cells, such as TNF-α and IL-6, are associated with up-regulation of acute-phase response proteins and suppression of CYP enzymes. For new biological entities, particularly immunomodulators, evaluating the potential for Kupffer cell activation is an emerging concept in preclinical development. Kupffer cells are estimated to comprise approximately 4-8% of total liver cell content and approximately 20% of non-parenchymal cells (Raccanelli and Rehermann, 2006). [Read more…]
Neurons, Astrocytes, Microglia: High Quality primary cells source
In the field of neurosciences, increasing research is being undertaken on neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases, as well as on nerve injury and regeneration. One of the challenges researchers face is finding the appropriate cellular neuromodels, as close as possible to the in vivo environment. Primary cells are one of the answers, increasingly used in co-culture systems and 3D models. However, cells from the nervous system are not readily accessible, nor are they easy to culture.
Cell Applications Inc. provide solutions to face these challenges, ranging from highly pure, low passage ready-to-use primary cells, to stem cells and induced pluripotent stem cells (iPSC) derived from a variety of clinically relevant species. Let’s take a look at a selection of their neuron, microglia and astrocyte models in relation to their potential applications.
[Read more…]
Cancer immunotherapy: explore the cytokine “milieu” with Quantibody 200 Biomarker Service
Autologous tumour cell vaccines vs. dendritic cell vaccines: What’s best, and why?
Understanding the best approach for tumour vaccinations is of growing importance in the personalized cancer immunotherapy field. Current models use a variety of treatments, but two include the use of irradiated autologous tumour cells (TCV), or autologous dendritic cells loaded with tumour associated antigens (DCV). In a randomized trial of metastatic melanoma patients undergoing either TCV or DCV, DCV patient survival was far superior at 43.4 vs 20.5 months. Why was the response more effective when the same antigens were provided to the immune response? Dillman, Robert O., et al. brought some answers in a paper published in the Journal for immunotherapy of cancer in 2018). Looking at the cytokine “milieu” with the Quantibody 200 Biomarker Microarray Service helped the authors in understanding the differences in vaccine responses. [Read more…]
Antibody reproducibility: what will make the difference…
Rockland Immunochemicals, Inc., (Rockland) provide the highest quality antibodies to the academic, biopharma, and diagnostic industries for use in basic research, assay development, preclinical and clinical studies, and bioprocessing. With facilities in Pennsylvania established since 55 years ago, Rockland manufactures products ideally suited for integration into critical assays such as western blotting, immunohistochemistry (IHC), immunofluorescence microscopy (IF), ELISA, flow cytometry, and 2D imaging. Their antibodies show remarkable quality and reproducibility from batch to batch. Their popular anti-RFP is one example out of many.
Demonstrating Rockland’s commitment in this matter (manufacturing antibodies of high quality and reproducibility), Rockland’s CSO, Dr. Carl Ascoli, testified at the US National Academies of Sciences, Engineering and Medicine’s third of six public sessions on Reproducibility and Replicability in Science on April 18th this year. [Read more…]
Maximize metabolic activities by limiting Hepatocyte cryoinjury
I am following up on my series of posts based on the work done by Chris Bohl and collaborators at Sekisui Xenotech. Here, he looks at the effect of cryopreservation on pooled hepatocytes metabolic activities, and how the patented Cryostax technology can address this issue.
DDI studies: New TransiPort cells for OATP1A2 and OATP2B1 transporters
Membrane transporters can have clinically relevant effects on the pharmacokinetics and pharmacodynamics of a drug in various organs and tissues by controlling its absorption, distribution and elimination. Together with metabolizing enzymes, they can drive a drug’s pharmacological action, as well as a drug can modulate transporter expression or activity, hence the importance of evaluating transporter-mediated drug-drug interactions recommended by the FDA guidelines. Genomembrane have developed transiently expressing ready-to-use cells to study FDA approved transporters (TransiPort). I had described this product range and their unique features in a previous post. I would like to introduce in this one 2 newly released cells overexpressing OATP1A2 and OATP2B1 transporters. [Read more…]
NADPH RapidStart regeneration system for long-term metabolism
NADPH is a critical cofactor supporting numerous biochemical reactions. In ADME-Tox studies, NAD(P)H regeneration is strongly recommended when using drug metabolizing enzymes (ex. Cytochrome P450 (CYP), Flavin-containing MonoOxygenases (FMO)), Recombinant CYPs (incl. bactosomes) or cellular fractions (Microsomes, S9). Currently, the most simple and cost-effective way to regenerate the NAD(P)H in situ and enzymatically is to use the commercially-available RapidStart™ NADPH Regenerating System (Xenotech-Sekisui).
RapidStart uses an enzymatic reaction that changes NADP to NADPH, which is then oxidized by CYPs back to NADP, and the cycle continues…
Assess catabolic stability of biologics & ADCs with Lysosomes – Characterised test systems
Following up on my series of posts based on Dr Chris Bohl’s work at Sekisui Xenotech, in this post I invite you to take a look at the work he has published, together with Dr Christopher Seib, Maciej Czerwinski, Zell Woodworth and David Buckley, Ph.D., illustrating the characterization of isolated human liver lysosomes, and validating them as test systems for in vitro assessment of catabolic stability of biologics drugs entering the cell by the endosomal–lysosomal pathway.
iPSC Research: specialized manufacturers for quality reagents
In a previous post, I introduced a selection of routine as well as innovative reagents for pluripotent stem cells (iPSC) research. Here, I’d like to present a few more interesting products, with a focus on several manufacturers specialized in this domain: Primorigen, Stemgent and Stemcultures.