Target Identification: Model for Gram- negative Sepsis

Description

The project “Target Identification” aims to investigate as yet unknown factors activated in the course of sepsis. Sepsis is defined as a spectrum of clinical conditions caused by an intense systemic immune response of the body to an infection and is characterised by systemic inflammation, including activation of the complement and coagulation systems. Extracorporeal adsorptive therapy makes it possible to interfere with the main targets in sepsis. Therefore, specific factors could be removed from patients’ blood to stop the course of sepsis and to stabilise their immune systems. Sepsis is a complex disease with many unknown and thus unidentified factors. This project should help to discover and identify such unknown factors and investigate the possible benefits of adsorption for patients. Another focus of this project is the establishment of an artificial blood vessel. Investigations of endothelial cell (EC) behaviour and EC interactions with different types of blood cells pose a challenge with respect to experimental design in cell culture models. Optimised growth conditions of cells and well-defined shear stress are critical in an in vitro system. Omitting these factors produces cell types that are not physiological, which leads to biased results and false interpretations. Therefore, a specially designed EC bioreactor that simulates natural human blood vascular conditions, particularly in terms of morphology, the growth pattern of ECs, and flow conditions, is necessary for the reconstitution and simulation of the natural blood vessels in vivo. The main objective of this project is to design and develop an EC culture model that could simulate blood vessel physiology. In this model, isolated human umbilical vein endothelial cells (HUVECs) line the inside surface of polysulfone (PS) tubing under a pulsatile flow in a bioreactor set-up that has separate “intra-vascular” and “extra-vascular” perfusion reservoirs. Additionally, smooth muscle cells (SMCs) form a confluent layer of cells on the outer capillary surface, while THP-1 monocytes are circulated through the system to mimic human blood flow.

Details

Duration 01/02/2008 - 31/12/2010
Funding Bundesländer (inkl. deren Stiftungen und Einrichtungen)
Program Technologieförderung NÖ
Department

Department for Biomedical Research

Center for Biomedical Technology

Principle investigator for the project (Danube University Krems) Mag. Dr. Dagmar Pfeiffer
Project members Dr. Giulia Mazza, MSc Eva Rossmanith

Publications

Pfeiffer, D.; Roßmanith, E.; Lang, I.; Falkenhagen, D. (2017). miR-146a, miR-146b, and miR-155 increase expression of IL-6 and IL-8 and support HSP10 in an in vitro sepsis model. PLoS ONE, 12(6): e0179850

Schwanzer-Pfeiffer, D.; Roßmanith, E.; Schildberger, A.; Falkenhagen, D. (2010). Characterization of SVEP1, KIAA, and SRPX2 in an in vitro cell culture model of endotoxemia. Cellular Immunology Vol. 263: 65-70

Maurer, B. (2010). Encapsulated monocytes as a treatment possibility for sepsis. Diploma Thesis

Mazza, G.; Schwanzer-Pfeiffer, D.; Ciechanowska, A.; Wojcicki, J.; Falkenhagen, D. (2009). Co-Cultivation and Stimulation of HUVEC and THP-1 Monocytes in Biomimetic Artificial Capillaries . Int J Art Org

Schwanzer-Pfeiffer, D.; Roßmanith, E.; Falkenhagen, D. (2009). Characterization of newly identified factors in a cell culture model of endotoxicemia. Shock

Schwanzer-Pfeiffer D, Ciechanowska A, Józwiak A, Hartmann J, Sabalinska S, Falkenhagen D, Wójcicki J (2002). Hodowla komòrek sródblonka na polisulfonowych membranach pólprzepuszczalnych plaskich i kapilarnych. XII Krajowa Konferencja Naukowa Biocybernetyka i Inz.

Lectures

A 2-step cell culture model: Influence of unknown factors in endotoxicemia

ESICM 2010, 01/01/2010

A Cell Culture Model to Analyze the Influence of Endotoxins on Changes in Gene Expression of Endothelial Cells

TSIS München 2010, 01/01/2010

Effect of Flow in a Dynamic Model of Endotoxemia, Based on a Hollow Fiber Bioreactor

TSIS München 2010, 01/01/2010

The Role of SVEP-1, KIAA and SRPUL in a Cell Culture Model of Endotoxaemia

SHOCK 2009, 25/09/2009

Co-Cultivation and Stimulation of HUVEC and THP-1 Monocytes in Biomimetic Artificial Capillaries

ESAO 2009, 05/09/2009

Team

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