Assessment of permeability in deep tissue capillaries using a new method reflects the nutrient supply status in a healthy heart.

Introduction: The in vitro organoid model is a valuable tool for studying organ development and disease. However, a key current challenge is the absence of a functional vascular compartment, which results from limited understanding of capillary function in vivo. Multisystem disorders involve physiological abnormalities that affect different organs in various ways. Notably, women have a higher prevalence of microvessel disease in the heart compared to men. This is because, until now, there has been no way to detect or evaluate the material exchange functions carried out by capillaries deep within healthy heart tissue. Methods: To detect fluorescent material leaking from intracardiac microvessels deep within the left ventricular wall under healthy conditions, female mice were injected with fluorescent dextran via the tail vein. The heart tissue was quickly removed, frozen, sliced, and examined directly under fluorescence. Additionally, the extent of the fluorescent substance diffusion was measured in young and aged female mice. Results: We observed fluorescent substances leaking from deep heart capillaries under healthy conditions. We then developed a method to measure capillary permeability by assessing the diffusion area. Furthermore, this method showed that the permeability of capillaries in the hearts of aged female mice was lower than that of young female mice. Conclusion: We have developed a method to assess capillary permeability in deep tissue. This research will improve our understanding of how capillaries exchange substances and support tissue function. This new method will not only provide new insights into studies of cardiac disease risk and sex differences, but also assist in developing more advanced in vitro models. It will further aid in refining the best cell transplantation techniques.