TY - JOUR
T1 - Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation
AU - Capotondo, Alessia
AU - Milazzo, Rita
AU - Politi, Letterio Salvatore
AU - Quattrini, Angelo
AU - Palini, Alessio
AU - Plati, Tiziana
AU - Merella, Stefania
AU - Nonis, Alessandro
AU - Di Serio, Clelia
AU - Montini, Eugenio
AU - Naldini, Luigi
AU - Biffi, Alessandra
PY - 2012/9/11
Y1 - 2012/9/11
N2 - 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.
AB - 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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U2 - 10.1073/pnas.1205858109
DO - 10.1073/pnas.1205858109
M3 - Article
C2 - 22923692
AN - SCOPUS:84866276426
VL - 109
SP - 15018
EP - 15023
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 37
ER -