Disclosed is a method for obtaining a population of human Treg cells including the steps of: (a) culturing a population of human monocytes with a medium including an amount of an interleukin-34 (IL-34) polypeptide in order to obtain a population of immunosuppressive macrophages; (b) co-culturing a population of human peripheral blood mononuclear cells (PBMCs) and the population of immunosuppressive macrophages obtained at step (a).

Disclosed herein are various embodiments relating to methods of producing iMGLs, for example, from pluripotent stem cells (PSCs), methods of using iMGLs, and compositions of iMGLs. Also disclosed herein are methods to study various neurological disorders, such as for studying Alzheimer's disease. In addition, disclosed herein are methods of investigating genotypic and phenotypic effects of microglia cells in various physiological and pathological environments in the CNS and brain.

A method of culturing an organoid includes combining a neural precursor cell with a first volume of a cortical media or a dopaminergic media to form an organoid. A microglia is then added to the organoid, and the combined organoid and microglia are added to a cryovial with a second volume of the cortical media or the dopaminergic media, and which includes an amount of IL-34 and GM-CSF and an amount of a buffering solution. The cryovial is subsequently sealed and the organoid is cultured for a pre-determined period of time under closed conditions. Systems for culturing an organoid include an organoid formed from a neural precursor cell, a microglia, an effective amount of a cortical media or a dopaminergic media, a buffering solution, and a cryovial for housing the aforementioned components under closed conditions.

The present invention provides methods and compositions for the generation of microglial progenitor cells and microglial cells from pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells. The present invention also provides cells produced using such methods, and both methods of treatment and methods of drug screening that use such cells. Also provided are various tissue culture media, tissue culture media supplements, and kits useful for the generation of human microglial progenitor cells and human microglial cells.

A composition for culturing peripheral blood monocyte-derived regulatory T cells includes at least one antibody selected from the group consisting of anti-CD2, anti-CD3, anti-CD7, anti-CD8, anti-CD28, anti-CD30L, anti-CD40, anti-CD70, anti-CD80, anti-CD83, and anti-CD86; at least one cytokine selected from the group consisting of interleukin-2, interleukin-4, interleukin-7, interleukin-12, interleukin-15, interleukin-34, and TGF-; and superoxide dismutase. A regulatory T cell culturing method using this composition is also provided. The regulatory T cells according obtained by this method can be utilized for treatment of autoimmune diseases.

Interleukin-34 is a cytokine that is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involvement of IL-34 has been shown in areas as diverse as neuronal protection, autoimmune diseases, infection, cancer, and transplantation. Recent work has also demonstrated a new and possible therapeutic role for IL-34 as a Foxp3.sup.+ Treg-secreted cytokine mediator of transplant tolerance. New mutated IL-34 polypeptides have been generated, which can be used as agonists or antagonists.

The present disclosure concerns a microglia progenitor cell derived from bone marrow and/or placental stromal cells and/or umbilical cord stromal cell and methods for their isolation; as well as use of said cells for therapy of disorders of the CNS.

The present invention provides methods and compositions for the generation of microglial progenitor cells and microglial cells from pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells. The present invention also provides cells produced using such methods, and both methods of treatment and methods of drug screening that use such cells. Also provided are various tissue culture media, tissue culture media supplements, and kits useful for the generation of human microglial progenitor cells and human microglial cells.