title: Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation.
abstract: 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.
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Capotondo
authors.forename: Rita
authors.initials: R
authors.lastname: Milazzo
authors.forename: Letterio Salvatore
authors.initials: LS
authors.lastname: Politi
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
authors.forename: Alessio
authors.initials: A
authors.lastname: Palini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Plati
authors.forename: Stefania
authors.initials: S
authors.lastname: Merella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nonis
authors.forename: Clelia
authors.initials: C
authors.lastname: di Serio
authors.forename: Eugenio
authors.initials: E
authors.lastname: Montini
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biffi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D020287:In Situ Nick-End Labeling; D020140:Lysosomal Storage Diseases, Nervous System / Q000628:therapy*; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology*; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D049452:Green Fluorescent Proteins