The present disclosure relates to compositions and methods for enhanced engraftment of hematopoietic cells into the brain, and to therapeutic methods of treating central nervous system (CNS) diseases and disorders in subjects where replacing CNS pot macrophages (including microglia) and other tissue-resident macrophages with donor cells would be beneficial. In particular, the present disclosure relates to the use of a microglia depleting agent to enhance engraftment of hematopoietic-derived macrophages in the brain of a subject undergoing hematopoietic cell transplantation, to treat a subject suffering from a leukodystrophy and undergoing hematopoietic cell transplantation, to treat a subject suffering from a disease mediated by microglial dysfunction and undergoing hematopoietic cell transplantation, and to related methods. The present disclosure also relates to detection within cell populations of beMcϕ and microglia signatures.
Compositions and Methods of Enhancing the Homing and/or Engraftment of Hematopoietic Cells in the Central Nervous System