MatTek EU team members will be in attendance at multiple conferences in Europe this month as an exhibitor, presenter, and sponsor. Dr. Jan Markus and Dr. Silvia Letasiova will be giving lectures on MatTek’s EpiIntestinal and EpiDerm tissue models. MatTek will also be presenting latest research and findings at additional meetings in June as well as sponsoring the 2nd Centro 3R Annual Meeting in Genova, Italy, June 20-21. Connect with us below to request more information on our talks, posters and research in the pipeline.
June 4 – 5 The School of Biosciences University of Cardiff, Wales
Dr. Jan Markus will be giving a talk titled Drug Toxicity and Permeability Screening Using a 3D Reconstructed Human Small Intestine Tissue Model. Dr. Markus’ presentation will take place during the Advanced Cell Culture; 3D, Fluid Flow & Co-culture session on Tuesday, June 4th. The talk will begin at 2:20 PM and discuss MatTek’s EpiIntestinal tissue model’s use for drug toxicity and permeability screening.
June 13 – 14 Rotterdam, The Netherlands
Dr. Jan Markus will be giving a talk on the second day of the conference during the Tox Screening and Enabling Technologies session and begin at 2:30 PM.
Prediction of Gastrointestinal Toxicity and Drug Absorption Using the Reconstructed 3D Model of Human Small Intestine Epithelium (EpiIntestinal).
Abstract: Small intestine is an important entry gateway for many nutrients, drugs and other substances. About 90% of orally administered drug absorption occurs in the small intestine. Thereby there is a need of good and reliable in vitro model capable to predict drug toxicity and absorption/metabolism patterns that would replace intestine models relying predominantly on the use of cell lines generated from the colon or kidney. The reconstructed 3D human small intestine model – EpiIntestinal mimics morphology and cell-type composition of normal human small intestine. It is polarized, allows studying bidirectional drug penetration through intestinal wall and expresses proteins involved in active drug transport and metabolism at physiological level. This allows modelling of complex drug absorption profiles, including the permeation, metabolism, drug-drug interaction and adverse effects of drugs on epithelium. Our results revealed that EpiIntestinal mimics the in vivo drug absorption profile much closer than the cancer cell line-based model. EpiIntestinal was also shown to predict toxicity with much higher specificity and sensitivity than the animal model. All in all, this model represents a promising tool to model complex processes occurring in small intestine.
June 17 – 20 Prague Congress Center Prague, Czech Republic
MatTek IVLSL will exhibit at this year’s meeting and are sponsoring the conference in Prague, Czech Republic. Dr. Jan Markus, Project Manager and Scientist at MatTek IVLSL, will present a lecture on MatTek’s EpiIntestinal human small intestine model, which excels as a method for evaluating toxicity, metabolism, drug absorption and compound efficacy in a preclinical testing environment.
Ligand-Induced Inflammation and Live Bacteria in the In Vitro Reconstructed 3D Model of Small Intestine Epithelium, will take place June 20 during Session 8: Future of Probiotics and Prebiotics and Delivery Vehicles. The session will be in the Forum Hall and last from 4 PM to 5:45 PM. Read the abstract below for a quick introduction of the talk’s topics.
Abstract: Epithelium of small intestine (SMI) is known to be involved in innate immune responses by recognizing potential pathogens through cellular pattern recognition receptors (PRRs). Here we present experiments utilizing the reconstructed 3D tissue model allowing studying these interactions in vitro. The SMI tissues are cultured using human primary intestinal enterocytes and fibroblasts and their 3-dimensional polarity and morphology mimics that of native in vivo tissues. Characterization of the SMI tissues included evaluation of structural features, barrier properties, and expression of drug transporters and drug metabolizing enzymes. The purpose of this study was to investigate PRR responses following exposure of SMI tissues to live bacteria or various Toll-like receptor (TLRs) and Nod-like receptor (NOD) ligands. Exposure of intestinal tissues to live bacterial (commensals and pathogens) or ligands to TLR4 (LPS) and NOD2 (Muramyl dipeptide; MDP) induced gene expression of pro-inflammatory cytokines such as IFN‑β, IL‑1β, IL‑6, and RANTES. Prolonged exposure of intestinal tissues to IL-1β also resulted in reduced membrane integrity and induction of pro-inflammatory cytokines known to stimulate acquired immune cell responses by inducing cytokine release such as IL-17, TNF-α, and IFN-Ƴ or by initiating the migration of inflammatory cells. All these responses may be precursors to IBD-like disease. To simulate the effect of acquired immune cell responses on the intestinal epithelium, we also exposed the tissues to combinations of TNF-α, IFN-g and IL-1 β, which compromised the barrier integrity and induced the release of pro-inflammatory cytokines. The effect of TNF-α and IFN-g on the intestinal epithelium was further exacerbated if antigen-presenting cells were incorporated into the 3D intestinal tissues. In summary, our results suggest that the EpiIntestinal tissue is capable of modelling innate immune responses and can be a useful tool to study the complex interactions of human intestinal epithelium with microbiome in vitro.
June 26 – 28 Hotel SITNO Vyhne, Slovakia
Posters: 11:20 – 12:40 SESSION 3 – IN VITRO TOXICOLOGY
Use of In Vitro Reconstructed Normal Human Epidermal Model EpiDerm and Interleukin-18 (IL-18) to Determine the Skin Sensitatizion Potency of Different Chemicals
Letasiova S.1, Galbiati V.2, Corsini E.2, Kandarova H.1 1 MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia 2 Laboratory of Toxicology, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Abstract: Determination of skin sensitization potential has traditionally been conducted in animal models, such as the Mouse Local Lymph Node Assay (LLNA) and the Guinea Pig Maximisation Test (GPMT). However, a growing focus and consensus for minimizing animal use have stimulated the development of in vitro methods to assess skin sensitization. Interleukin-18 (IL-18) release in reconstructed human epidermal models has been identified as a potentially useful endpoint for the identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability (1, 2). The aim of this study was to investigate the impact of the modality of chemical exposure on the predictive capacity of the assay. EpiDerm tissue viability assessed by MTT assay and IL-18 release assessed by ELISA were evaluated after 24 h topical exposure to test chemicals directly applied to the surface of EpiDerm. DPBS and/or acetone: olive oil (4:1) were used as vehicles. A total of 20 chemicals were tested. The testing set included 11 senzitizers and 9 non senzitizers. Two independent dose – response experiments were conducted, resulting in correct prediction of the sensitizing potency of test chemicals. The assessment of IL-18 release using in vitro reconstructed normal human epidermal model EpiDerm appears to be a promising tool for in vitro determination of contact sensitization potential.
Modeling of Drug Toxicity and Absorption Using the Reconstructed Human Small Intestine Epithelium
Markus J1, Landry T2, Stevens Z2, Klausner M2, Armento A2 and Ayehunie S2. 1MatTek In Vitro Life Science Laboratories, Mlynske Nivy 73, Bratislava, Slovakia 2MatTek Corporation, 200 Homer Avenue, Ashland MA, USA.
Abstract: Majority of orally administered nutrients, drugs and other substances enter blood flow in the small intestine. To predict drug toxicity and absorption/metabolism patterns one needs a good and reliable in vitro model. Most of currently available in vitro intestine models are neither organ nor species-specific, relying predominantly on the use of cell lines generated from the colon or kidney. In addition they lack a proper 3D architecture and functionality, which in turn affects their ability to properly predict drug absorption and toxic effects. Here we present the reconstructed 3D human small intestine model – EpiIntestinal, which mimics morphology and cell-type composition of normal human small intestine. As opposed to organoid models, EpiIntestinal is polarized and allows studying bidirectional drug penetration through intestinal wall. It expresses proteins involved in active drug transport and metabolism at physiological levels, which makes it ideal for modelling of complex drug absorption profiles, including the permeation, metabolism, drug-drug interaction and adverse effects of drugs on epithelium. Comparative studies revealed that the absorption of drug in EpiIntestinal mimics the in vivo profile much closer than the currently used Caco-2 model. In another study aimed at adverse effects of drugs, EpiIntestinal was able to predict toxicity with much higher specificity and sensitivity than animal model. All in all, this model represents a promising tool to model complex processes occurring in small intestine.