Sailor KA, Agoranos G, López-Manzaneda S, et al. Hematopoietic Stem Cell Transplantation Chemotherapy Causes Microglia Senescence and Peripheral Macrophage Engraftment in the Brain. Nature Medicine. 2022; (doi: 10.1038/s41591-022-01691-9).
Researchers believe chemotherapy undertaken before hematopoietic stem cell transplantation (HSCT) explains why the post-transplant brain contains peripheral engrafted parenchymal macrophages that are not present in the normal brain. The engraftment mechanism has been a mystery until now, but scientists have a newfound understanding of the process as it occurs in mice. HSCT chemotherapy used for pretransplantation myeloablation triggers microglia senescence and a gradual reduction in microglial density to a critical level. The study authors posit that microglia in the brain are stripped of their regenerative abilities, including permanent loss of adult neurogenesis, but that donor macrophages subsequently fill this void.