Provided herein are, in various embodiments, methods and compositions for differentiating olfactory mucosa-derived mesenchymal stem cells (OM-MSC). In certain embodiments, the disclosure provides for media to differentiate OM-MSCs. In still further embodiments, the disclosure provides for methods and compositions using differentiated OM-MSCs for the treatment of nerve repair. In particular embodiments, the disclosure provides for novel treatments of peripheral nerve repair.

The present disclosure provides methods and compositions for microglia replacement therapy in a subject in need thereof. In some cases, the method involves administering myeloid cells to the central nervous system of a subject. In some cases, the myeloid cells are derived from embryonic or extraembryonic tissue. In some cases, the myeloid cells are genetically modified. The genetic modification may include a colony stimulating factor 1 receptor (CSF1R) variant that is resistant to a CSF1R inhibitor, yet retains sensitivity to its ligand (e.g., CSF1, IL34).

The present specification provides a method of producing induced functional astrocytes (iAs) from human pluripotent stem cells substantially more rapidly than previously achieved. These iAs express biomarkers and have functional characteristics typical of natural astrocytes. The iAs are useful in the exploration of astrocyte biology, pathophysiology, and in models of neurologic diseases and disorders.

Methods for differentiating human pluripotent stem cells to dorsal neuroectoderm progenitors and further to glial progenitor cells and oligodendrocyte progenitor cells (OPCs) using inhibitors of BMP signaling and MAPK/ERK signaling are provided. Also provided are cells and cellular compositions obtained by such methods, and uses of such cells. Further provided are methods and protocols for efficiently differentiating human pluripotent stem cells to OPCs in the absence of the ventralizing morphogen SHH or a SHH signaling activator. The methods of the present disclosure reproducibly produce dorsal neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

According to one embodiment, a pluripotent stem cell manufacturing system includes processing circuitry. The processing circuitry acquires storage information for the storage of a sample from a donor, and surviving cell number information for the number of surviving cells contained in the sample. The processing circuitry estimates tissue stem cell number information for the number of tissue stem cells contained in the sample, based on the storage information and the surviving cell number information.

The purpose of the present invention is to efficiently produce microglia from pluripotent stem cells. Provided is a method for producing microglia from pluripotent stem cells, comprising the following steps: (a) a step of co-culturing a pluripotent stem cell together with a feeder cell for 7 days or longer, and obtaining a blood progenitor cell; (b) a step of co-culturing the blood progenitor cell obtained in step (a) together with a feeder cell in the presence of IL-3 and/or GM-CSF, and obtaining an embryonic monocyte; and (c) a step of, in the presence of M-CSF, co-culturing the embryonic monocyte obtained in step (b) together with an astrocyte, or culturing the embryonic monocyte using an astrocyte supernatant.

The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.

A pharmaceutical composition for suppressing neuro-inflammation; a pharmaceutical composition for assisting transplantation of neuron precursor cells, pluripotent stem cells, and/or neurons; a pharmaceutical composition for promoting the stabilization of Nrf2 protein in glial cells; a pharmaceutical composition for protecting nerve cells from neuro-inflammation are provided. Provided is a pharmaceutical composition containing, as an active ingredient, a compound having an inhibiting ability against phosphorylation activity of DYRK1A protein, or a pharmaceutically acceptable salt of the compound.

The present invention comprises a system and method for co-culturing glia cells and neurons in a combination of glia culture medium and neuron medium wherein the glia cells and neurons have cell morphology, cell reactions and/or cell interactions that exist in vivo after the co-culturing for up to about 21 days, up to about 30 days, up to about 40 days, up to about 45 days. Since the cell morphology, cell reaction and/or cell interaction of the co-culture are similar to those seen in vivo, the present system is capable of being configured as animal models for research, drug screening, testing and conducting clinical trials.

The present disclosure features CX3CR1 hemizygous and/or homozygous defective cells and methods of using such cells for the treatment of a metabolic or neurological disorder. The disclosed methods include methods for making and modifying CX3CR1 hemizygous and/or homozygous defective cells, such as hematopoietic stem progenitor cells. Other disclosed methods include methods of treating a subject having or suspected of having a metabolic or neurological disease comprising administering to the subject a composition comprising a hemizygous and/or homozygous defective CX3CR1 cell. The CX3CR1 hemizygous and/or homozygous defective cell may be modified to have a nucleic acid molecule encoding a therapeutic polypeptide or polynucleotide.