NDLI: Targeting Myeloid Cells to the Brain Using Non-Myeloablative Conditioning

Content Provider	PubMed Central
Author	Böttcher, Chotima Francisco, Fernández-klett Nadine, Gladow Rolfes, Simone Priller, Josef
Editor	Marc, Tjwa
Copyright Year	2013
Abstract	Bone marrow-derived cells (BMDCs) are able to colonize the central nervous system (CNS) at sites of damage. This ability makes BMDCs an ideal cellular vehicle for transferring therapeutic genes/molecules to the CNS. However, conditioning is required for bone marrow-derived myeloid cells to engraft in the brain, which so far has been achieved by total body irradiation (TBI) and by chemotherapy (e.g. busulfan treatment). Unfortunately, both regimens massively disturb the host’s hematopoietic compartment. Here, we established a conditioning protocol to target myeloid cells to sites of brain damage in mice using non-myeloablative focal head irradiation (HI). This treatment was associated with comparatively low inflammatory responses in the CNS despite cranial radiation doses which are identical to TBI, as revealed by gene expression analysis of cytokines/chemokines such as CCL2, CXCL10, TNF-α and CCL5. HI prior to bone marrow transplantation resulted in much lower levels of blood chimerism defined as the percentage of donor-derived cells in peripheral blood (< 5%) compared with TBI (> 95%) or busulfan treatment (>50%). Nevertheless, HI effectively recruited myeloid cells to the area of motoneuron degeneration in the brainstem within 7 days after facial nerve axotomy. In contrast, no donor-derived cells were detected in the lesioned facial nucleus of busulfan-treated animals up to 2 weeks after transplantation. Our findings suggest that myeloid cells can be targeted to sites of brain damage even in the presence of very low levels of peripheral blood chimerism. We established a novel non-myeloablative conditioning protocol with minimal disturbance of the host’s hematopoietic system for targeting BMDCs specifically to areas of pathology in the brain.
Related Links	http://dx.doi.org/10.1371/journal.pone.0080260
Starting Page	80260
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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