Project Objectives

• Learn efficient and reliable protocols for the expansion and differentiation of human induced pluripotent stem cells (hiPSCs).
• Acquire hands‑on expertise in differentiating hiPSCs into cardiomyocytes with high, reproducible efficiency.
• Learn non‑invasive methods to assess cardiomyocyte differentiation stage and subtype (e.g. ventricular or atrial).
• Establish the differentiation protocol at the Home Lab (University of Basel) for in‑house production of hiPSC‑derived cardiomyocytes.
• Integrate hiPSC‑derived cardiomyocytes into 3D fibrin‑gel engineered cardiac tissues.
• Study the effects of cardiac maturation, hypoxia, nutrient deprivation, and responses to mechanical and electrical stimulation on cardiomyocyte maturation and functionality.

3Rs Impact

• Reduces the use of neonatal rats previously required to isolate primary cardiomyocytes for proof‑of‑principle experiments.
• Enables the partial replacement of animal‑derived cardiomyocytes with human iPSC‑derived cardiomyocytes in engineered heart models.
• Reduces the number of animals exposed to severe (SD3) in vivo cardiac procedures, such as thoracotomy and coronary artery ligation.
• Improves the scientific relevance of cardiac disease models, potentially reducing exploratory animal experiments in later stages.

Background

Understanding how cardiomyocytes (cardiac muscle cells) mature from a fetal‑like to an adult phenotype is essential for research on cardiac disease, damage, and repair. At the Home Lab (University of Basel) engineered 3D cardiac tissues have been developed to allow modelling of healthy and diseased myocardium (the muscular tissue of the heart). While these models have proven useful, their translational relevance is limited by the availability and maturity of cardiomyocytes used, which have often been derived from neonatal animal sources, such as rats.

To address this, Dr Sileo will learn robust protocols for the expansion and differentiation of human induced pluripotent stem cells (hiPSCs) into cardiomyocytes. The Host Lab (University Medical Center Hamburg Eppendorf), led by Prof. Thomas Eschenhagen, has considerable expertise in engineered heart tissue technologies and with large‑scale, well‑characterised cardiomyocyte differentiation. As a result of this knowledge exchange, Dr Sileo therefore aims to generate reproducible, mature human cardiomyocytes at the Home Lab, and to use them to create 3D engineered tissues, which will facilitate more human-relevant cardiac maturation studies.