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Neurosci Lett. 2015 Feb 19;588:196-201. doi: 10.1016/j.neulet.2015.01.023. Epub 2015 Jan 9.

Submyeloablative conditioning with busulfan permits bone marrow-derived cell accumulation in a murine model of Alzheimer's disease.

Author information

1
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Dr., Burnaby, BC V5A 1S6, Canada.
2
Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
3
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Dr., Burnaby, BC V5A 1S6, Canada. Electronic address: ckrieger@sfu.ca.

Abstract

Previous work has suggested that bone marrow (BM)-derived cells (BMDCs) accumulate within the CNS and could potentially associate with β-amyloid plaques in Alzheimer's disease (AD). To explore the accumulation of BMDCs in murine AD, we transplanted green fluorescent protein (GFP)-labeled BM cells into triple transgenic (3×Tg) and wild-type (wt) mice using non-irradiative myelosuppresive conditioning with busulfan (BU). We find that BU (80mg/kg) is sufficient to obtain adequate chimerism (>85%) in wt mice. In order to obtain appreciable non-irradiative chimerism in the 3×Tg mice (>80%), anti-asialo ganglio-N-tetraosylceramide (α-ASGM-1) antibody was also used to reduce natural killer cell function and thereby abrogate the hybrid resistance of the 3×Tg mouse strain. Using BU conditioning and α-ASGM-1 together, we observed sustained BM chimerism and BMDC accumulation within the CNS of the 3×Tg and wt mice. In cortex and hippocampus, BMDC accumulation was perivascular in distribution and similar between 3×Tg and wt mice, with no clear association between BMDCs and AD plaques. We conclude that non-irradiative BM chimerism can be achieved with BU in 3×Tg mice, but requires α-ASGM-1 (or similar appropriate NK-cell depletion). Use of this chimerism protocol permits BMDCs accumulation in the CNS of mixed strain recipient mice although BMDCs appear to be largely perivascular within cortex and hippocampus.

KEYWORDS:

3×Tg mice; Bone marrow-derived cells; Busulfan; Busulfex; Chimerism; Hybrid resistance

PMID:
25582787
DOI:
10.1016/j.neulet.2015.01.023
[Indexed for MEDLINE]

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