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Publication : Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation.

First Author  Capotondo A Year  2012
Journal  Proc Natl Acad Sci U S A Volume  109
Issue  37 Pages  15018-23
PubMed ID  22923692 Mgi Jnum  J:190040
Mgi Id  MGI:5447876 Doi  10.1073/pnas.1205858109
Citation  Capotondo A, et al. (2012) Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation. Proc Natl Acad Sci U S A 109(37):15018-23
abstractText  The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.
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