Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation
Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation
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DOI：
10.1073/pnas.1205858109
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发表时间：
2012-09-11
影响因子：
11.1
通讯作者：
Biffi, Alessandra
中科院分区：
文献类型：
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作者：
Capotondo, Alessia;Milazzo, Rita;Biffi, Alessandra
最近的假设是，出生后的小胶质细胞通过出生前定殖于大脑的局部前体独立于循环单核细胞维持，这对治疗各种神经系统疾病具有相关意义，包括溶酶体贮积症（LSD），对于LSD，应用造血细胞移植（HCT）以用表达缺陷性功能水解酶的细胞重建受体骨髓腔室，包括小胶质细胞。通过研究野生型和LSD小鼠在不同的时间点后，HCT，我们显示了短期波的脑浸润的发生由一部分移植的造血祖细胞，独立于管理的准备方案和从存在的疾病状态在大脑中。然而，只有使用能够消融功能定义的脑驻留髓样前体细胞的预处理方案，才能通过早期移民的局部增殖介导小胶质细胞与供体的周转，而不是从循环中进入成熟细胞。
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.