ESR 11: Generation of a patient-specific in vitro model of cardiac fibrosis for personalized anti-fibrotic drug screening.
Project Title: Generation of a patient-specific in vitro model of cardiac fibrosis for personalized anti-fibrotic drug screening.
Objectives: The ESR will interact with a multidisciplinary team of cardiologists, tissue engineers and cell biologists in order to design a patient-specific 3D in vitro model of cardiac fibrosis. The project is aimed at (a) analyzing in vivo the ratio between cardiac fibroblasts and cardiomyocytes during the fibrotic process, (b) the fibrotic index of the tissue (c) the biophysical parameters of the decellularized extracellular matrix obtained from fibrotic tissue. The biophysical parameters retrieved from the patients will be integrated in the in vitro model by regulating the proportion of patient-derived cardiac fibroblasts and iPSC cardiomyocytes, and determining the proper concentration and crosslinking of the encapsulating biomimetic hydrogel.
The model will be validated as a drug screening platform, to test not only canonical compounds modulating Angiotensin-renin-aldosterone system and TGF-β pathway, but also new pharmacological targets.
Expected Results: The in vitro model of custom-tailored cardiac tissue will be the first of its kind due to the ability to integrate both specific biomechanical cues and cellular composition from a given patient in a holistic way. Thanks to its reasonably low cost, highly adaptable features, as well as the suitability to test stimuli in a very controlled environment as compared to the animal models, it will serve as a valuable tool for drug screening in order to determine the most effective personalized treatment.
Main Supervisors: Giancarlo Forte (FNUSA-ICRC), Paolo Maiuri (IFOM)
Duration: 36 months
Planned Secondment: EOC (3 months) to acquire knowledge in developing models of fibrosis during the first year, POLIMI (2 months) during second year to learn protocols for hydrogel micro and macrofabrication.
Enrolment in Doctoral Degree: PhD in Medical Biology at Masaryk University, Brno (Czech Republic)
For any specific requests on this project, please get in contact with Prof. Giancarlo Forte (Giancarlo.firstname.lastname@example.org)