Gudrun Dandekar

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

Epithelial-to-mesenchymal transition (EMT) is discussed to be centrally involved in invasion, stemness, and drug resistance. Experimental models to evaluate this process in its biological complexity are limited. To shed light on EMT impact and test drug response more reliably, we use a lung tumor test system based on a decellularized intestinal mat...

Nanodiamonds (ND) have been suggested to have several potential uses in biomedicine, since they are seemingly biocompatible. However, data about the biological effects of ND in physiological conditions are scarce. In this study, we observed that prostate cancer cells (LNCaP) and breast cancer cells (MDA-MB-231 and MCF-7) cultured with ND show morph...

Treatment of terminal heart failure still poses a significant clinical problem. Cardiac tissue engineering could offer autologous solutions for the replacement of non-functional myocardial tissue. So far, soft matrix construction and missing large scale prevascularization prevented the application of sizeable cardiac repair patches. We developed a...

Background Immunotherapy with chimeric antigen receptor (CAR)-engineered T-cells is effective in some hematologic tumors. In solid tumors, however, sustained antitumor responses after CAR T-cell therapy remain to be demonstrated both in the pre-clinical and clinical setting. A perceived barrier to the efficacy of CAR T-cell therapy in solid tumors...

To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment respon...

Solid tumors impose immunological and physical barriers to the efficacy of chimeric antigen receptor (CAR) T-cell therapy that are not reflected in conventional pre-clinical testing against singularized tumor cells in two-dimensional culture. Here, we established microphysiologic three-dimensional (3D) lung and breast cancer models that resemble ar...

Precision medicine has changed thinking in cancer therapy, highlighting a better understanding of the individual clinical interventions. But what role do the drivers and pathways identified from pan-cancer genome analysis play in the tumor? In this letter, we will highlight the importance of in silico modeling in precision medicine. In the current...

Curcumin (CUR)is a natural extract from the plant Curcuma longa and part of turmeric, a spice and herbal remedy in traditional medicine. Thousands of papers claim a plethora of health benefits by CUR, but a growing number of reports and contributions caution that many experimental data may be artifacts or outright deny any suitability of CUR due to...

Patient‐tailored therapy based on tumor drivers is promising for lung cancer treatment. For this we combined in vitro tissue models with in silico analyses. Using individual cell lines with specific mutations we demonstrate a generic and rapid stratification pipeline for targeted tumor therapy. We improve in vitro models of tissue‐conditions by a b...

Tissue engineering is a promising field, focused on developing solutions for the increasing demand on tissues and organs regarding transplantation purposes. The process to generate such tissues is complex, and includes an appropriate combination of specific cell types, scaffolds, and physical or biochemical stimuli to guide cell growth and differen...

This manuscript describes a ultra-high loaded nanoformulation of curcumin. This compound is extremely water insoluble but could be dissolved using poly(2-oxazoline)/poly(2-oxazine) based polymer amphiphiles. The resulting formulations were thoroughly characterized in solution and solid form by NMR, dynamic light scattering, electron microscopy, HPL...

MicroRNAs are well-known strong RNA regulators modulating whole functional units in complex signaling networks. Regarding clinical application, they have potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21 promotes and microRNA-34 inhibit...

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)

Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimens...

In the present study, we combined an in vitro 3D lung tumor model with an in silico model to optimize predictions of drug response based on a specific mutational background. The model is generated on a decellularized porcine scaffold that reproduces tissue-specific characteristics regarding extracellular matrix composition and architecture includin...

Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to...

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...

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...

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...

Cancer is one of the leading causes of death world-wide. For drug screening and development, appropriate tumor models are needed that reflect the situation in the patient robustly and accurately. Next to the identification of new compounds, cancer research contributes to the understanding of complex tumor biology. This enables targeted and individu...

The last decade saw an alarming increase in antibiotic resistance in infections, with more than 13 million deaths per year from infections. Counter strategies include hygiene, antibiotic restriction and new antibiotics such as quinupristin, linezolid, tigecycline, daptomycin and dalbavancin. Presently, pharmacogenomics with basic research is reveal...

This review summarizes some of the new trends in the fight against drug resistant bacteria. We review Gram-positive (e.g., S.aureus) and Gram-negative (e.g., Pseudomonas aeruginosa, Helicobacter pylori) bacteria, the current antibiotic resistance situation, as well as resistance spread and some recently discovered resistance mechanisms, such as tho...

The EphB ligand ephrinB2 has been identified as a critical determinant of arterial endothelial differentiation and as a positive regulator of invading endothelial cells during angiogenesis. This study was aimed at identifying determinants of endothelial cell ephrinB2 expression. Arteriovenous asymmetrical endothelial cell ephrinB2 expression in viv...

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Contact-dependent interactions between endothelial cells (ECs), as well as between ECs and mural cells, play a key role in the formation of a regular vascular system and the assembly of the vessel wall. Recent studies have identified ephrinB2 and EphB4 as markers and makers of arteriovenous differentiation during vascular development. On the basis...

Tightening of endothelial cell-to-cell contacts is an important event at the end of angiogenesis in order to achieve controlled transfer of solutes between the blood stream and solid tissues. We found that tightening of endothelial cell-to-cell contacts and the formation of a permeability barrier can be induced in vitro by dibutyryl cAMP and hydroc...