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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\u2010specific macrophage characteristics, they retained persistent molecular differences from na\u00efve 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.<\/jats:p>","DOI":"10.1002\/advs.202519669","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:27:05Z","timestamp":1786699625000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mr BMT Achieves Systemic Macrophage Replacement With Preservation of Tissue Homeostasis"],"prefix":"10.1002","volume":"13","author":[{"given":"Yufei","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Laboratory Animal Center Institute for Translational Brain Research State Key Laboratory of Brain Function and Disorders MOE Frontiers Center for Brain Science Fudan SANS Neuroscience Center Fudan University Shanghai China"},{"name":"Department of Neurosurgery, Huashan Hospital MOE Innovative 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