Advanced human models of the heart to understand cardiovascular disease

Introduction

Cardiovascular diseases (CVD) are the cause of the highest mortality and morbidity rates worldwide and are expected to increase in coming years, leading to epidemic proportions. Traditional experimental in vitro and animal models are not predictive enough, which hampers the emergence of novel therapies for the treatment of CVD.

Need for Human Models

Consequently, there is an urgent need to establish realistic human models that lead to a better understanding of CVD, providing the opportunity to identify and validate druggable targets.

Project Overview

In Heart2Beat, I will develop innovative human heart models for mimicking cardiovascular disease. I will use an innovative in-air microfluidic platform for ultra-high throughput encapsulating of human pluripotent stem cells in microgels to generate self-organized multicellular 3D human cardiac organoids that replicate the architectural design of the human heart.

Integration of Technologies

Furthermore, I will integrate and develop innovative technologies from the fields of human stem cell biology and engineering to create 3D (micro)-engineered heart tissues, coupled to a versatile and automated microfluidic platform. This will enable the assessment of multifunctional analysis, including:

1. Contraction
2. Relaxation
3. Metabolism
4. Morphology

Functional Human Mini-Heart

Finally, I will build a functional human mini-heart with the capacity to pump fluid, which is the main function of the human heart, and then assess clinically relevant readouts in healthy and diseased conditions.

Innovative Pipeline

These first-of-its-kind advanced 3D human cardiac models and platforms are complementary to each other and form a highly innovative and comprehensive pipeline for modeling human CVD. This will enable (ultra)high throughput screening and in-depth multifunctional pre-clinical analysis of healthy and diseased heart tissues.

Impact on Medicine

Successful implementation of Heart2Beat will provide insight into mechanisms of disease and will initiate a paradigm shift for personalized medicine and drug discovery, leading to tailor-made therapy for patients suffering from CVD.