There is provided a method of inducing differentiation of bone marrow stromal cells to neural cells or skeletal muscle cells by introduction of a Notch gene. Specifically, the invention provides a method of inducing differentiation of bone marrow stromal cells to neural cells or skeletal muscle cells in vitro, which method comprises introducing a Notch gene and/or a Notch signaling related gene into the cells, wherein the finally obtained differentiated cells are the result of cell division of the bone marrow stromal cells into which the Notch gene and/or Notch signaling related gene have been introduced. The invention also provides a method of inducing further differentiation of the differentiation-induced neural cells to dopaminergic neurons or acetylcholinergic neurons. The invention yet further provides a treatment method for neurodegenerative and skeletal muscle degenerative diseases which employs neural precursor cells, neural cells or skeletal muscle cells produced by the method of the invention.

Techniques and systems are disclosed for a bioassay that is an in vitro mimic of peripheral nerve generation using the sensory neurons that innervate the peripheral nervous system. In some embodiments, the techniques may assist in detecting the bioactivity or potency of nerve grafts (e.g., processed, acellular human allografts) for fostering or supporting peripheral nerve regeneration. In various embodiments, techniques comprise affixing neurons (e.g., a DRG) to a nerve graft segment to form a test construct; culturing the test construct in a medium; analyzing the test construct to indicate the amount of outgrowing nerve structure; and determining the potency of the nerve graft from a metric derived from the analysis. In some embodiments, techniques and materials may be used to test the effect of a varied test condition on nerve growth.

The present disclosure provides methods of lineage specific differentiation of pluripotent stem cells, including induced pluripotent stem cells, into floor plate midbrain progenitor cells, determined dopamine (DA) neuron progenitor cells, and/or DA neurons. Also provided are compositions uses thereof, such as for treating neurodegenerative diseases and conditions, including Parkinson's disease.

The present invention is directed to a system including neurons over-expressing UBB+1, organized in a 3-dimensional culture, and method of using same. A process for making the system of the invention is also provided.

Human striatal and midbrain organoids or spheroids are generated in vitro, which may be generated at least in part from human pluripotent stem (hPS) cells. Such spheroids model the regions of the human brain and comprise specific sets of cells that are associated with the striatum, including mature medium spiny neurons, and midbrain of a human, and that can be subsequently assembled with the cortex to form cortico-striatal-midbrain circuits in vitro.

The invention relates to a genetically modified mouse comprising a heterozygous mutation of Tardbp (TDP-43) gene in that the Asn at amino acid 390 in TDP-43 is substituted with an amino acid that is different from Asn, wherein the genetically modified mouse exhibits Amyotrophic lateral sclerosis (ALS)-like phenotypes, TDP-43 proteinopathies and/or motor neuron degeneration. The invention also so relates to an isolated spinal cord motor neuron differentiated from an embryonic stem cell (ESC) that is obtained from an offspring of a genetically modified mouse according to the invention. Methods for identifying an agent alleviating and/or suppressing ALS-TDP pathogenesis are also disclosed.

High-yield mammalian transient expression systems can include a cell culture media (particularly serum free, non-animal derived, and/or chemically defined media) for introducing macromolecules and compounds (e.g., nucleic acid molecules) into cells (e.g., eukaryotic cells). Cells containing such introduced materials can then be cultured in the cell culture media. In particular, the invention allows introduction of nucleic acid molecules (e.g., vectors) into cells (particularly mammalian cells) and expression of proteins encoded by the nucleic acid molecules in the cells. The invention obviates the need to change the cell culture medium each time a different procedure is performed with the cells (e.g., culturing cells vs. transfecting cells). The invention also relates to compositions and kits useful for culturing and transforming/transfecting cells.

Provided is a method for efficiently manufacturing high-purity peripheral nerve cells from undifferentiated cells. The method for manufacturing peripheral nerve cells from undifferentiated cells having an ability to differentiate into peripheral nerve cells includes the following steps (a) and (b): (a) culturing undifferentiated cells having an ability to differentiate into peripheral nerve cells to induce differentiation into neural progenitor cells without detaching a grown colony from a culture vessel; and (b) detaching the neural progenitor cells produced in the step (a) from the culture vessel, then seeding the cells at a seeding density of 2×10.sup.5 to 6×10.sup.5 cells/cm.sup.2 to a culture vessel, and culturing the cells for 14 to 42 days.

Disclosed herein are neural extracellular vesicles (EVs) and methods of using these EVs in the treatment of spinal cord injury, stroke, and traumatic brain injury and neurodegenerative disease.

The present invention relates to a method for in-vitro production of mammalian neurons expressing the 6 isoforms of the Tau protein (2N4R, 1N4R, 0N4R, 2N3R, 1N3R, 0N3R), comprising a step of neuronal differentiation, in which cellular microcompartments are cultivated for a period of 5 weeks to 100 weeks, each one comprising a hollow hydro gel capsule surrounding post-mitotic neuronal cells and an extracellular matrix, the neuronal differentiation step being carried out in a bioreactor, the cellular microcompartments being kept in suspension in an enclosure of the bioreactor containing a neuronal differentiation medium.