In mice, bone marrow method replaces macrophages in organs

In Fudan University’s latest mouse study, donor bone-marrow cells moved beyond the brain and replaced resident macrophages in the liver, kidney, lung and spleen. The replacement lasted at least 9 months, while the organs kept their tissue integrity and core biological functions. It is a broader test of a technique first designed to reach the brain’s hard-to-replace immune cells.

Traditional bone marrow transplantation, or tBMT, can replace marrow that produces faulty or cancerous immune cells. But donor immune cells usually engraft poorly in the central nervous system, including microglia, the specialized macrophages that support the brain. Fudan’s method is called microglia replacement by bone marrow transplantation, or Mr. BMT.

The method begins with PLX5622, a molecule that blocks CSF1R, a receptor that helps existing microglia survive. Depleting those cells before transplantation creates open niches for donor bone-marrow cells. In this study, the same process also enabled donor-derived macrophages to settle in peripheral organs.

The results were similar to tBMT for macrophage engraftment in the organs examined. Mr. BMT also preserved the innate immune response after exposure to LPS, a molecule found in the outer membrane of bacteria such as E. coli and Salmonella. The new cells were initially slow to acquire the gene-expression profile of local macrophages, but their macrophage-signature gene expression recovered over time; the team presumes this period allowed them to adapt to local tissue environments.

Concretely, the work suggests that one transplant strategy could eventually address diseases involving immune cells in both the brain and the rest of the body. Yanxia Rao and Bo Peng of Fudan University describe the findings as evidence that tissue function remained largely intact after transplantation. The limit is equally clear: this safety evidence comes from mice, and the team still hopes the approach will translate into safe, effective treatment in humans.