Three-Dimensional Visualization of the Cardiac Stroma.

Cardiac tissue engineering is a promising strategy to restore cardiac function in heart failure patients. Understanding the cardiac tissue architecture including the cardiac stroma is essential for developing not only advanced cardiac tissue engineering but also novel therapeutic strategies. One of the crucial components of the cardiac stroma is the myocardial vasculature. To enhance the spatial visualization of the cardiac stromal cytoarchitecture with a particular focus on myocardial vasculature, we performed 3D reconstructions of the murine cardiac micro vessels using Serial Block-Face Scanning Electron Microscopy (SBF-SEM). These analyses revealed that pericyte cell bodies were primarily oriented lengthwise and extended several cellular protrusions towards the endothelium. At capillary branching points, some pericytes made contact with both capillaries emerging from branching. In addition to pericytes that are completely encapsulated by the common basal lamina together with capillary endothelial cells, we identified other vascular-associated cells located outside this sheath. Based on marker expression, these cells were distinguished from fibroblasts and suggested to be telocytes. The vascular-associated cells formed electron-dense contact zones with endothelial cells, suggesting functional coupling between these both cell types. In conclusion, this study provides detailed three-dimensional visualizations of the cardiac stroma with a particular focus on cardiac microvasculature, offering enhanced insight into the cardiac stromal cytoarchitecture.