title: Bone marrow cell recruitment to the brain in the absence of irradiation or parabiosis bias.
abstract: The engraftment of bone marrow-derived cells has been described not only during diseases of the central nervous system (CNS) but also under healthy conditions. However, previous studies pointing to an ample bone marrow cell engraftment used irradiation-induced bone marrow chimeras that evoked severe alterations of the CNS micromilieu including disturbances of the blood brain barrier (BBB), damage of endothelial cells and local induction of proinflammatory cytokines. On the other hand, parabiosis experiments using temporarily joined circulatory systems generally yielded low levels of myeloid cell chimerism thereby potentially underestimating bone marrow cell turnover with the CNS. To avoid these drawbacks we established a protocol using the alkylating agent busulfan prior to allogenic bone marrow transplantation from CX3CR1(GFP/+) donors. This regimen resulted in a stable and high peripheral myeloid chimerism, significantly reduced cytokine induction and preserved BBB integrity. Importantly, bone marrow cell recruitment to the CNS was strongly diminished under these conditions and only weakly enhanced during local neurodegeneration induced by facial nerve axotomy. These results underscore the requirement of local CNS conditioning for efficient recruitment of bone marrow cells, establish busulfan as an alternative treatment for studying bone marrow chimeras and suggest a critical re-evaluation of earlier chimeric studies involving irradiation or parabiosis regimens.
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kierdorf
authors.forename: Natalie
authors.initials: N
authors.lastname: Katzmarski
authors.forename: Carola A
authors.initials: CA
authors.lastname: Haas
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D002066:Busulfan / Q000494:pharmacology; D002465:Cell Movement; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019653:Myeloablative Agonists / Q000494:pharmacology; D010227:Parabiosis; D011828:Radiation Chimera; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists; D002066:Busulfan