Research Scope

Cardiac myocytes are the archetypic cell population of the heart, and they drive cardiac electro-mechanical function. Accordingly, cardiomyocytes have traditionally formed a focus of heart research. However, while cardiomyocytes make up around two-thirds of cardiac tissue by volume, they are dwarfed in terms of cell numbers by non-myocytes, including fibroblasts, immune cells including tissue-resident macrophages, or endothelial cells. It is becoming increasingly clear that non-myocytes and the extracellular matrix are crucial determinants of cardiac structure and function in health, ageing, and disease.

Non-myocytes are found in three tissue sub-types of the myocardium: (i) the coronary vascular/ lymphatic system, (ii) the intracardiac nervous system, and (iii) the interstitium. The interstitium (literally, ‘that what stands in-between’) is made up of components such as fibroblasts , tissue-resident macrophages, and extracellular matrix. It provides structural stability to the heart, integrates cardiomyocytes with the coronary/ lymphatic and the intracardiac nervous systems, and generates a signalling microenvironment that is crucial for homeostasis of individual cells and the heart as a whole. Given this importance, it is surprising how little is known about the interstitium (including the lack of a universally accepted definition), its (auto-)regulation, and its functional relevance for the heart. Our research unit (‘Forschungsgruppe’: FOR) plans to investigate the role of the interstitium for cardiac electrical and mechanical activity by characterising interstitial non-myocytes, extracellular matrix, and their interactions with each other and with cardiomyocytes , in healthy and remodelling myocardium, with the long-term vision of laying a new, interstitium-aware foundation for steering cardiac structure and function for patient benefit.

Our vision builds on understanding the (patho-)physiological role of the interstitium as a structural and functional entity, based on a multi-level, multi-parametric, multi-dimensional and multi-disciplinary research approach, enabled by teams with excellent research track records and a robust collaborative spirit, to generate the knowledge and tools needed to steer cardiac interstitial dynamics and their effects on heart function in health, ageing and disease. Ultimately, we are working towards a quantitative and mechanistic understanding of how the interstitium holds – the heart together in its inmost folds.¹

Defining the Interstitium as the Focus of FOR 6051

The term ‘interstitium’ may benefit from clarification, as it has evolved over many centuries, carrying different connotations, depending on research context. Our FOR 6051 uses the following ‘physio-anatomical’ definition:
The interstitium is a tissue constituent that encompasses non-nerval and non-vascular cells, ECM, and extracellular fluid (ECF) in the space between those cells of an organ that underlie its main physiological function.

The cardiac interstitium represents a highly dynamic myocardial tissue component of key importance for normal heart structure and function (A), whose disease-induced remodelling includes diffuse interstitial (B) and focal replacement fibrosis (C). TATS: transverse/ axial tubular system; components not to scale.