Compositions and methods for microglia replacement therapy

A method for microglia cell replacement therapy, wherein the method comprises:

• (a) introducing a microglial cell inhibitor into a central nervous system (CNS) of a subject in need thereof, thereby inactivating, suppressing, or depleting a native microglial cell population of the subject in need thereof;
• and
• (b) introducing a composition into the CNS of the subject in need thereof,
• wherein the composition comprises a myeloid cell:
• (i) comprising a receptor tyrosine kinase that comprises a mutation that reduces the sensitivity of the receptor tyrosine kinase to the microglial cell inhibitor, and
• (ii) has the potential to differentiate into a microglia-like cell, and
• wherein the myeloid cell replaces the native microglial cell population by differentiating into a microglia-like cell in vivo.