Biodistribution of in vitro-derived microglia applied intranasally and intravenously to mice: effects of aging

Background aims. The age of both the donor and the recipient has a potential influence on the efficacy of various cell therapies, but the underlying mechanisms are still being charted. We studied the effect of donor and recipient age in the context of microglia migration. Methods. Microglia were in vitroedifferentiated from bone marrow of young (3 months) and aged (12 months) mice and transplanted into young (w3 months) and aged (w17 months) C57BL/6 mice (n ¼ 25) through intravenous and intranasal application routes. Recipients were not immune-suppressed or irradiated. Transplanted microglia were tracked through the use of a sex-mismatched setup or histologically with the use of cells from enhanced green fluorescent protein enhanced green fluorescent protein transgenic mice. Results. No acute rejections or transplant-associated toxicity was observed. After 10 days, both intravenously and intranasally transplanted cells were detected in the brain. Transplanted cells were also found in the blood and the lymph system. The applied cells were also tracked in lungs and kidney but only after intravenous injection subjected to a “pulmonary first-pass effect.” After 28 days, intravenously delivered cells were also found in the bone marrow and other organs, especially in aged recipients. Whereas in young recipients the transplanted microglia did not appear to persist, in aged brains the transplanted cells could still be identified up to 28 days after transplantation. However, when cells from aged donors were used, no signals of transplanted cells could be detected in the recipients. Conclusions. This study establishes proof of principle that in vitroederived microglia from young but not from aged donors, intravenously or intranasally transplanted, migrate to the brain in young and aged recipients.