Vivarium and Biosafety - Track C, Use of Organoids and Advanced Cardiac Cultures for Animal Reduction and Translational Acceleration

• Grant number: 25/07938-1
• Support Opportunities: Research Infrastructure Program - Improvement of the Operational Infrastructure of Small-Animal Facilities and Biosafety
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Eduardo Krieger
• Grantee: José Eduardo Krieger
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• City of the host institution: São Paulo

Abstract

This project proposes the development of an integrated platform combining human heterocellular cardiac organoids derived from hiPSCs (induced pluripotent stem cells) and ex vivo cultures of human and porcine cardiac tissue, for use in translational cardiology research. The initiative aims to enhance animal facility infrastructure in line with the 3Rs principles (Replacement, Reduction, Refinement), by reducing the use of experimental animals through advanced alternative models.Specifically, we will establish heterocellular cardiac organoids that mimic human myocardium and maintain cardiac tissue slices in culture for up to two weeks under controlled mechanical and electrical stimulation. The combined use of these in vitro models is expected to partially replace animal models, reduce the number of animals required in preclinical studies, and accelerate the translation of scientific discoveries to clinical application, increasing the reliability and human relevance of the results.The availability of systems such as MyoDish (biomechanically and electrically stimulated culture chambers) and IonOptix (instrumentation for measuring contraction force and intracellular calcium) will be crucial for obtaining functional data from cultured cardiac tissue, in addition to high-content structural and functional parameters already accessible in the laboratory. This innovative infrastructure will provide a more ethical and predictive human cardiac model, improving drug screening and disease modeling while reducing reliance on animal models. The proposal is fully aligned with the 3Rs framework and with the goals of the FAPESP call for the improvement of animal research facilities. (AU)