• CD105 + small vessels undergo age-related thinning and fragmentation along the femoral shaft • The vascular branching of larger CD31 hi vessels in the femur increases with age The vasculature within the bone marrow plays a pivotal role in shaping the hematopoietic environment, significantly influencing the development and function of blood cells. Yet, the intricate shifts in vascular architecture, especially as the body ages or under physiological stress, remain largely uncharted territory. In this study, we explored these vascular dynamics using light sheet fluorescence microscopy paired with advanced image analysis, focusing on both large, CD31 hi , and smaller, CD105 + vessels within murine femora. We compared young adult (8-week) mice to moderately aged (52-week) mice and assessed the impact of hematological stress induced by prior blood sampling. Our findings revealed an intriguing balance of resilience and adaptability: Larger vessels show a remarkable structural stability across ages, while smaller vessels undergo pronounced age-associated remodeling. In aged mice, vascular branching complexity surges, with higher branch density and narrower vessel diameters in specific femur regions—clear hallmarks of vascular aging. Interestingly, even after prior blood sampling, the bone marrow vasculature maintains its integrity, hinting at a robust resilience to hematological stress. This resilience underscores the potential to streamline research models by reusing animals for both cell isolation and histology, supporting the 3R principles to minimize animal use. These insights into the stability, adaptability, and regional-specific remodeling of bone marrow vasculature, highlighting its remarkable resilience, provide a deeper understanding of age-related vascular remodeling, and offer valuable implications for experimental design in hematopoiesis research.
Hemmen et al. (Sun,) studied this question.