Mr BMT Achieves Systemic Macrophage Replacement With Preservation of Tissue Homeostasis.

Microglia replacement is a novel and clinically validated therapeutic framework for brain diseases. Microglia replacement by bone marrow transplantation (Mr BMT) is among the most widely used strategies, achieving efficient replacement and robust therapeutic efficacy. However, Mr BMT affects not only the brain but also the peripheral system. In this study, we comprehensively investigated its effects on peripheral organs, including the liver, kidney, spleen, and lung. We found that Mr BMT achieved robust and sustained macrophage replacement across multiple organs. Although the replaced macrophages broadly acquired organ-specific macrophage characteristics, they retained persistent molecular differences from naïve resident macrophages, suggesting that macrophage identity is simultaneously shaped by the local microenvironment and developmental ontogeny. Despite molecular remodeling to some extent, overall tissue architecture and biological function were preserved after Mr BMT. Together, our findings demonstrate that Mr BMT establishes durable systemic macrophage replacement in peripheral organs while preserving overt tissue homeostasis.