Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy.

ABSTRACT: Microglia replacement strategies are increasingly being considered for the treatment of primary microgliopathies like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, available mouse models fail to recapitulate the diverse neuropathologies and reduced microglia numbers observed in patients. In this study, we generated a xenotolerant mouse model lacking the fms-intronic regulatory element (FIRE) enhancer within Csf1r, which develops nearly all the hallmark pathologies associated with ALSP. Remarkably, transplantation of human induced pluripotent stem cell (iPSC)-derived microglial (iMG) progenitors restores a homeostatic microglial signature and prevents the development of axonal spheroids, white matter abnormalities, reactive astrocytosis, and brain

SUBMITTER: Chadarevian JP 

PROVIDER: S-EPMC12357648 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature