Research Funding "Tandem Projects"

The aim of the third project "iPSC-based sensitive neurons as an animal-free model of translational pain and neurodegeneration research" by Dr. Christian Schinke, Dr. Narasimha Swamy Telugu and Dr. Valeria Fernandez Vallone is to use human stem cell derived sensory neurons to research sensory loss and altered pain perception of patients after chemotherapy. After chemotherapy, many people suffer from neurological side effects such as altered sensation, sensory loss or pain: a so-called chemotherapy-induced polyneuropathy. Research in the field of this neurological disorders has so far mainly been carried out in animals. In this project, the trio from the Department of Neurology, the Max Delbrück Centre and the BIH seek to develop an animal-free model for translational research into pain and neurotoxicity: Based on sensory neurons derived from patients with and without severe neuropathy, induced pluripotent stem cells (iPSC) will be generated and differentiated into sensory neurons. Changes in protein and cell metabolism caused by chemotherapy will be analysed experimentally and correlated with the clinical complaints of the patients. The aim is to identify the individual mechanisms of neurotoxicity and pain, to promote iPSC-based methods to replace animal experiments and to significantly reduce animal-based knockout models in pain research.

Figure: Study design of iPSC-derived sensory neurons as an animal-free model for translational pain and neurodegeneration research. The project combines a clinical study with basic research: Patients who undergo chemotherapy are recruited from the CICARO study. According to their clinical symptoms, white blood cells from patients with severe neuropathy and without neuropathy are reprogrammed into induced pluripotent stem cells (iPSC) and differentiated into sensory neurons. These neurons are then challenged with chemotherapy in a dish. Using an integrated multi-omic approach, we analyze changes in the metabolism and protein expression in the cells which may underly sensory loss or pain in the patient. (Copyright: Dr. Valeria Fernandez Vallone)

The aim of the project "Personalised treatment planning using matrix-based in vitro liver metastases of colorectal carcinoma to reduce metastatic mouse models" is to develop better ex vivo cancer models and thereby reduce the number of experiments with mice. To achieve this, the two young scientists Dr. Karl Herbert Hillebrandt from the Surgical Clinic Campus Virchow-Klinikum and Dr. Björn Papke from the Institute of Pathology combine their expertise in the production of complex human tissues with research on 3D cancer models. Currently, 50 percent of patients with colorectal carcinoma also develop liver metastases as part of their disease. In order to better understand the individual behaviour of these colorectal liver metastases, the environment of the tumour cells within and around a metastasis must be mirrored as closely as possible. For this purpose, individual liver metastases are grown in vitro in the patient's decellularised liver matrix - i.e. a part of the liver tissue that has been freed from all cells. These individual matrix-based liver metastases are then used for personalised testing of different therapies. The two scientists hope that by successfully establishing this method, a large number of tumour mouse models can be dispensed with in the future.

Figure: Workflow from liver resection of a CRLM patient to its personalized drug screen without metastatic mouse models. (Copyright: Björn Papke und Karl Hillebrandt)

In order to develop a new method for the early detection of heart failure, Dr. Jana Grune and Dr. Bianca Nitzsche from the Institute of Physiology combine two already established methods in the project "Simulation of Heart failure in Ovo With Microscopy and Echocardiography (ShowMe)": the assessment of heart performance by means of ultrasound/microscopy and the use of fertilised chicken eggs. The aim is to detect cardiotoxic effects unambiguously and at an earlier stage of heart development than to date. In preclinical research on heart failure, the testing of cardiotoxic effects of drugs, foreign substances and pathogens is currently carried out almost exclusively in animal experiments on mice or rats. The two scientists now want to develop an alternative test system with the help of which the use of laboratory animals can be dispensed with. To this end, the already established in ovo model of fertilised chicken eggs is to be used and further developed in such a way that the potential cardiotoxicity of an active substance can in future already be determined in the chicken egg. If successful, it would also be possible to apply ShowMe in other areas in which small animals are currently used as standard for recording cardiac function.

Figure: ShowMe-Interaction of the gas exchange organ (chorioallantoic membrane), the lungs, with the ventricles. (Copyright: Grune/Nitzsche)