The cardiac interstitium comprises a heterogeneous population of cells relevant to adult heart muscle homeostasis. The detailed embryonic origin, quantitative and qualitative composition of cardiac interstitial cells remains unknown. By means of cell lineage tracing technologies, we have mapped the cellular components of the murine developing interstitium from the embryo to postnatal stages. Our results demonstrate that embryonic epicardial-derived cells (EPDC) pioneer the colonization of the interstitial space in the developing heart, displaying a typical transmural patterning across cardiac chamber walls. This study indicates that most EPDC remain at the cardiac interstitium in the form of fibroblastic(-like) cells, dynamically interacting with other non-epicardial-derived cells (e.g. bone marrow-derived cells). Using a variety of in vitro assays, we have characterized subpopulations of EPDC following criteria related to their molecular profile and mobilization properties (cell adhesion; proteolytic activity).
From our data we conclude that:
1) EPDC are the first cells that populate the cardiac interstitium, where they home and remain along adulthood; 2) EPDC display a unique proteolytic program from early stages of cardiac development and 3) these cells might be instrumental to the homing of other cell types late in development/postnatal life.
In summary, our work provides new information on the biology of cardiac interstitial cells (most specially cardiac fibroblasts), offering clues to understand paracrine and/or autocrine signals, as well as the ECM-related mechanisms (protein deposition and proteolysis), involved in clinically relevant patophysiological phenomena like ventricular remodeling after myocardial infarction.