Abstract: The present disclosure provides myeloid cells, microglial progenitor cells, and microglia-like cells in which a mutant gene has been repaired or replaced, and methods of using such cells to treat disease. Mutations in CSF1R were corrected in human induced pluripotent stem cells. The resulting cells were differentiated into microglial progenitors and then transplanted into the brain of xenotransplantation-compatible CSF1R-AFIRE/AFIRE mice, thereby preventing or reversing phenotypes associated with leukodystrophy, including thalamic microbleeds, calcification, astrogliosis, axonal spheroids, synaptic loss, and accumulation of Tau phosphorylated at threonine residue 217.

Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.

Abstract: Modified cells that express and present or secrete at least one therapeutic molecule that can treat or ameliorate a disease of interest such as but not limited to Alzheimer's disease. In the modified cells, expression of the therapeutic molecule is induced when the modified cells are proximate to or in contact with pathology related to the disease of interest. The present disclosure also relates to compositions and kits comprising the disclosed cells. The present disclosure also relates to methods of using the disclosed cells for treating disease.

Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.

Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.

Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.