The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells (e.g., human stem cells) into proprioceptors, proprioceptors generated by such methods, and compositions comprising such proprioceptors. The presently disclosed subject matter also provides for uses of such proprioceptors for preventing and/or treating disorders of proprioceptor neurons and/or neurodegenerative disorders (e.g., Friedreich's Ataxia).

Described herein is the use of CSF, more particularly external CSF or CSF-like compositions for the treatment and prevention of different diseases. More particularly, the application provides for the administration of CSF to the intrathecal space or the cerebral ventricles of a patient to increase intracranial pressure and/or CSF flow.

Described herein is the use of CSF, more particularly external CSF or CSF-like compositions for the treatment and prevention of different diseases. More particularly, the application provides for the administration of CSF to the intrathecal space or the cerebral ventricles of a patient to increase intracranial pressure and/or CSF flow.

Disclosed herein are methods of delivering a polypeptide, e.g., an antibody or antigen binding portion thereof, to the central nervous system of a subject, by administering to the subject the polypeptide (e.g., antibody or antigen-binding portion thereof) conjugated to the surface of an extracellular vesicle (EV) derived from a neural cell, e.g., a neural progenitor cell or a neural stem cell. Conjugates comprising neural EVs coupled to a polypeptide, such as an antibody or antigen binding portion thereof, and methods of use thereof, are also provided. Also disclosed herein are methods of delivering a polypeptide, e.g., an antibody or antigen binding portion thereof, by administering to the subject the polypeptide (e.g., antibody or antigen-binding portion thereof) loaded within the lumen of an extracellular vesicle (EV) derived from neural cells.

Disclosed herein are methods of delivering a polypeptide, e.g., an antibody or antigen binding portion thereof, to the central nervous system of a subject, by administering to the subject the polypeptide (e.g., antibody or antigen-binding portion thereof) conjugated to the surface of an extracellular vesicle (EV) derived from a neural cell, e.g., a neural progenitor cell or a neural stem cell. Conjugates comprising neural EVs coupled to a polypeptide, such as an antibody or antigen binding portion thereof, and methods of use thereof, are also provided. Also disclosed herein are methods of delivering a polypeptide, e.g., an antibody or antigen binding portion thereof, by administering to the subject the polypeptide (e.g., antibody or antigen-binding portion thereof) loaded within the lumen of an extracellular vesicle (EV) derived from neural cells.

Provided herein are methods for obtaining populations of reprogrammed MO-homeostatic tolerogenic microglial cells. The methods include providing an initial population of monocytes, e.g., peripheral blood monocytes (PBMC), from a subject, and reprogramming the cells by maintaining the PBMC in culture ex vivo in the presence of a sufficient amount of transforming growth factor-beta (TGFβ) and interferon-gamma (IFNγ) for a time and under conditions sufficient for the cells to become M0-homeostatic tolerogenic microglia. Also provided are methods of use of these cells, e.g., for the treatment of neurodegenerative diseases associated with inflammation, e.g., Alzheimer's Disease (AD); Multiple Sclerosis (MS), e.g., progressive MS; and Amyotrophic Lateral Sclerosis

Provided herein are methods for obtaining populations of reprogrammed MO-homeostatic tolerogenic microglial cells. The methods include providing an initial population of monocytes, e.g., peripheral blood monocytes (PBMC), from a subject, and reprogramming the cells by maintaining the PBMC in culture ex vivo in the presence of a sufficient amount of transforming growth factor-beta (TGFβ) and interferon-gamma (IFNγ) for a time and under conditions sufficient for the cells to become M0-homeostatic tolerogenic microglia. Also provided are methods of use of these cells, e.g., for the treatment of neurodegenerative diseases associated with inflammation, e.g., Alzheimer's Disease (AD); Multiple Sclerosis (MS), e.g., progressive MS; and Amyotrophic Lateral Sclerosis

Provided is a method for freezing a cell aggregate including neural cells. Provided is a method for freezing a cell aggregate including neural cells and having a three-dimensional structure, which comprises following steps (1) and (2): (1) soaking the cell aggregate including neural cells in a cryopreservation solution at 0° C. to 30° C. prior to freezing to prepare a cryopreservation solution-soaked cell aggregate; and (2) freezing the cell aggregate including neural cells in vapor phase of a liquid nitrogen container having a temperature of −150° C. or less.

Provided is a method for freezing a cell aggregate including neural cells. Provided is a method for freezing a cell aggregate including neural cells and having a three-dimensional structure, which comprises following steps (1) and (2): (1) soaking the cell aggregate including neural cells in a cryopreservation solution at 0° C. to 30° C. prior to freezing to prepare a cryopreservation solution-soaked cell aggregate; and (2) freezing the cell aggregate including neural cells in vapor phase of a liquid nitrogen container having a temperature of −150° C. or less.

Disclosed herein are nerve xenografts and methods of using such for repairing and/or protecting a nerve tissue in a human patient. The subject matter disclosed herein generally relates to nerve xenografts derived from genetically engineered source animals, and use of such nerve xenografts for repairing and/protecting nerve tissue in a human patient, e.g., for reconstruction of large peripheral nerve gaps, treatment of spinal cord injuries and ailments, and other therapies.