CNS Repopulation by Hematopoietic-Derived Microglia-Like Cells Corrects Progranulin deficiency.

ABSTRACT: Hematopoietic stem cell transplantation can deliver therapeutic proteins to the CNS through donor-derived hematopoietic cells that become microglia-like cells. However, using standard conditioning approaches, hematopoietic stem cell transplantation is currently limited by low and slow engraftment of microglia-like cells. We report an efficient conditioning regimen based on Busulfan and a six-day course of microglia depletion using the colony-stimulating factor receptor 1 inhibitor PLX3397. Combining Busulfan-myeloablation and transient microglia depletion results in robust, rapid, and persistent microglia replacement by bone marrow-derived microglia-like cells throughout the CNS. Adding PLX3397 does not affect neurobehavior or has adverse effects on hematopoietic reconstitution. Through si

SUBMITTER: Colella P 

PROVIDER: S-EPMC10543302 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature