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).
As is already known, multiple families of small GTPases (Ras, Arf and Rho families) make up the Ras GTPase superfamily. Due to their role as molecular switches in cell signalling (active GTP-bound state vs inactive GDP-bound states) and in many other cellular responses (cytoskeletal reorganization, regulation of transcription, apoptosis…), these small GTPases are the subject of intense investigation to try to understand the mechanisms that regulate activation and inactivation of this proteins.
In this post, I invite you to discover a revolutionary way to study these cell signalling events by quantifying the level of active small GTPases in your experimental model.
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.
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.
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