Journal
CELL TRANSPLANTATION
Volume 21, Issue 6, Pages 1149-1159Publisher
COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096368911X593154
Keywords
Microglia; Central nervous sysem (CNS); Neuroimmunology; Hematopoietic stem cell; Irradiation; Chemotherapy; Bone marrow-derived cells; Innate immunity
Funding
- Canadian Institutes for Health Research [219561]
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Understanding how bone marrow-derived cells (BMDCs) enter the central nervous system (CNS) is critical for the development of therapies for brain-related disorders using hematopoietic stem cells. We investigated the brain damages and blood-brain barrier (BBB) modification following either whole-body irradiation or a myeloablative chemotherapy regimen in mice, and the capacity for these treatments to induce the entry of BMDCs into the CNS. Neither treatment had a lasting effect on brain integrity and both were equally efficient at achieving myeloablation. Injection of bone marrow cells from green fluorescent protein (GFP) transgenic mice was able to completely repopulate the hematopoietic niche in the circulation and in hematopoietic organs (thymus and spleen). However, GFP(+) cells only entered the brain following whole-body irradiation. We conclude that myeloablation, damages to the brain integrity, or the BBB and peripheral chimerism are not responsible for the entry of BMDCs into the CNS following irradiation.
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