Partners of SP2 will be involved in defining protocols for harmonisation of experimental and clinical conditions, procedures for the screening of liver patients, sample collection and storage, as well as quality control.
Clinical scientists participating in WP 6 will identify a set of relevant drugs used in their clinical practice, known for their risks of inducing hepatic or cardiac toxicity. Organ biopsies, blood and urine samples will be taken from patients treated with these drugs. They will collaborate with WP5 to select these relevant drugs which will be used in vitro 3D models. Heart and liver spheroids will be exposed to the same set of drugs, and here, the list of chemicals will be expanded with further hepatic and cardiac toxicants carefully selected based on open source information, ultimately leading to several tens of drugs to be tested in vitro.
Samples from in vitro studies and patients will be sent to Sub-project 3 for molecular and functional analyses, with the aim of identifying biochemical patterns capable of anticipating the susceptibility and extent of hepatotoxic damage induced by drugs.
Partner HULAFE will participate as well in WP7 performing metabolomic studies both from in vitro experiments as well in clinical samples. It will participate in WP8 performing intracellular calcium measurements in cultures treated with the cardiotoxic drugs of interest.
In patients with cardiac toxicity, routine phenotypic analysis will include baseline patient characteristics, previous medical history, including cardiovascular symptoms induced by drug treatment and description of those. Imaging will obligatorily include echocardiography, ECG, and cardiac MRI if possible. These data obviously will strengthen the upgrading of the physiological heart model.
All data on clinical chemistry and histopathology will be collected and together with patient-related meta data sent to WP12, to collaborate in the analysis and relevance of clinical data.