David Fecher

University of Wuerzburg | JMU · Chair of Tissue Engineering and Regenerative Medicine

Background Sepsis is one of the leading causes of mortality in intensive care units, and sedation in the intensive care unit during sepsis is usually performed intravenously. The inhalative anesthetic sevoflurane has been shown to elicit protective effects in various inflammatory studies, but its role in peritonitis-induced sepsis remains elusive....

Treatment of malignant pleural mesothelioma (MPM) remains challenging as the tumor is diagnosed at a late stage and only inadequately responds to chemotherapy and radiation [3]. Furthermore the incidence of MPM will increase worldwide over the next years [3]. Preclinical testing proves to be difficult due to a lack of appropriate in vitro tumor mod...

Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and –testing. In the present study, we generated a complex 3D lung tumor test system based on acellular ra...

Evaluation of extracellular matrix (ECM) components in decellularized lung scaffolds. (A) Acellular lungs generated by SDS- and CHAPS-protocols tend to contain a lower amount of collagen per mg dry tissue than the scaffolds generated with Triton-SDC or H2O-SDC. While these exhibited significantly higher collagen content than native rat lungs (p = 0...

Evaluation of decellularization protocols. (A) The percentage of airspace in the decellularized matrices was compared to native lungs to quantify the structural preservation for different decellularization protocols. While scaffolds generated using Triton-SDC and H2O-SDC exhibited similar values to native tissue, the CHAPS- and SDS scaffolds showed...

Histologic assessment of extracellular matrix components in the decellularized lung matrices. All scaffolds showed similar and global retention of the basement membrane components collagen IV and fibronectin. In contrast, a reduced intensity for collagen I and elastin was observed in scaffolds generated with the SDS- and CHAPS– protocols. This was...

Schematic illustration of the different decellularization protocols used in this study. Each protocol utilizes a different perfusion pressure, volume or duration, respectively. Noteworthy, the SDS- and CHAPS-protocols use only the vascular system as the route of application. Protocols employing Triton-SDC and H2O-SDC apply decellularization solutio...

Separated and sectioned rat lung for analysis. Decellularized and native lung tissue was processed as depicted here to allow different analyses with one scaffold. Except for ultrastructural studies, each analysis was performed with tissue pieces of each part of the lung. The specific use of the single tissue pieces is listed in S1 Table. (TIF)

Antibodies used for immunohistochemical staining and immunofluorescence. (PDF)

Analyses performed with different tissue pieces of the lung. (PDF)

The potential of preclinical tumor models to predict the outcome of substances in the clinic is limited. More advanced models that include features of living tissues and parts of the microenvironment are urgently needed. At the chair of “Tissue Engineering and Regenerative Medicine” (TERM) and the Translational Center “Regenerative therapies in onc...

Zielsetzung: Das Verstandnis der Signalwege von Lungentumorgeweben ist die Voraussetzung fur die Entwicklung neuer und individualisierter Behandlungsstrategien. Methode: Tumorzellen zweier Zelllinien mit unterschiedlichem EGF-Rezeptor-Mutationsstatuts (A549 & HCC827) wurden auf einer auf der dezellularisierten, biologischen Tragerstruktur SISmuc au...

In vitro test systems have to be optimized to reduce preclinical failure rates. Therefore, we have introduced a new innovative system which mimics physiological conditions and enables vascularisation in bioreactors. Thus, we have developed test systems for intestinal uptake studies, for airway infections and for different tumour entities, e. g. lun...

Supplementary Figure S2TGFβ stimulation. Dynamic model simulation of different nodes of the signaling network (Figure 4A) using SQUAD. TGFβ‐receptor stimulation (initial value of TGFβ: 1.0), results in EMT signaling (0.9, nearly maximal), the activity of several other network nodes is shown in the cell‐type specific context and activation state of...

Supplementary data

Supplementary Figure S3Gefitinib effects on HCC827 in the 3D tumor tissue model. In 3D conditions the EGFR activation is reduced and apoptosis is induced in HCC827 by gefitinib. Immunohistochemical stainings of 3D tumor tissue models show weak signals for the EGFR in A549 (A, B) with no obvious phosphorylation (E, F). In HCC827 the EGFR could be cl...

Supplementary Figure S1In silico modeling of gefitinib response in A549 cells bearing a Kras mutation. Dynamic model simulation of different nodes (assuming constantly hyperactive Kras at 0.4) of the signaling network (Figure 4A) using SQUAD. (A) An activating signal of the EGFR (value: 0.3; EGF approximately 0.4, not strong, wild type) evokes a mo...

Background During reverse transcription, retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. To express full-length transcripts, retroviruses have to suppress polyadenylation in the 5′LTR and activate polyadenylation in the 3′LTR. Foamy viruses have a unique...

For the development of new treatment strategies against cancer, understanding signaling networks and their changes upon drug response is a promising approach to identify new drug targets and biomarker profiles. Pre-requisites are tumor models with multiple read-out options that accurately reflect the clinical situation. Tissue engineering technolog...