RAPID COMMUNICATION Kinetics of Central Nervous System Microglial and Macrophage Engraftment: Analysis Using a Transgenic Bone Marrow Transplantation Model

To determine the kinetics of tissue macrophage and microgwere observed. Alveolar macrophage engraftment was evident by 2 months and had increased to 61% of total tissue lial engraftment after bone marrow (BM) transplantation, we have developed a model using the ROSA 26 mouse. macrophages at 1 year posttransplantation. The kinetics of liver Kupffer cell engraftment were similar to those seen in Transplanted ROSA 26 cells can be precisely identified in recipient animals because they constitutively express b-gathe lung. However, donor microglial engraftment remained only 23% of total microglia at 6 months and increased to lactosidase (b-gal) and neomycin resistance. B6/129 F2 mice were irradiated and transplanted with BM from ROSA 26 only 30% by 1 year. Also, donor microglia were predominantly seen at perivascular and leptomeningeal, and not padonors and their tissues (spleen, marrow, brain, liver, and lung) examined at various time points to determine the kirenchymal, sites. The data show that microglia derive from BM precursors but turn over at a significantly slower rate netics of engraftment. Frozen sections from transplanted animals were stained histochemically for b-gal to identify than other tissue macrophages. No clinical or histological graft-versus-host disease was observed in the recipients of donor cells. At 1, 2, 6, and 12 months posttransplantation, 98% to 100% of granulocyte-macrophage colonies were of ROSA 26 BM. These kinetics may impact strategies for the gene therapy of lysosomal storage diseases. Because indidonor (ROSA 26) origin determined by b-gal staining and by neomycin resistance. Splenic monocytes/macrophages vidual donor cells can be identified in situ, the ROSA 26 model should have many applications in transplantation biwere 89% donor origin by 1 month confirming quick and complete engraftment of hematopoietic tissues. At this ology including studies of homing and differentiation. q 1997 by The American Society of Hematology. time, only rare ROSA 26 tissue macrophages or microglia