Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

A method of promoting neural stem cell differentiation is provided comprising exposing neural stem cells to a dopamine D.sub.4 receptor antagonist.

The present invention relates to a microfluidic device (1) for cultivating cells, in particular for generating brain organoids, comprising at least two fluid channels (2) positioned essentially opposite to each other and a main chamber (3) located between the fluid channels (2), wherein the main chamber (3) comprises at least one preferably sealable access opening, and each of the at least two fluid channels (2) is fluidly connected to the main chamber (3) at at least one point of contact (4), wherein a slotted structure (5) is provided at each point of contact (4) separating the main chamber (3) from the respective fluid channel (2), wherein the slotted structure (5) is permeable to a liquid.

Provided herein are compositions and methods describing the generation and use of in vitro pro-organs using microparticle scaffolds.

Provided are methods and compositions for transdifferentiation of a somatic cell, e.g., a fibroblast to a dopaminergic precursor, Specifically, provided are induced dopaminergic (iDP) cells, or master transcription factors (TFs) therefore, methods for making iDP cells, and methods and compositions for using them in, e.g., treating neurodegenerative diseases such as Parkinson's disease.

The present invention provides substantia nigra organoids on silica iSECnMs and method of producing the same. The present invention also provides method of cell therapy including the substantia nigra organoids on silica iSECnMs. It also provides a method of promoting differentiation of neural stem cells to neurons includes culturing the neural stem cells on a nanostructure having a plurality of nanozigzags or nanohelices fabricated from SiO.sub.2 or TiO.sub.x.

The present invention provides a method for inducing differentiation of pluripotent stem cells into neural precursor cells, comprising culturing the pluripotent stem cells in the presence of a small, molecule BMP inhibitor, and induced neural precursor cells prepared by this method.

The present invention provides a method for producing neural cells or a neural tissue, including the following steps (1)-(3): (1) a first step of culturing pluripotent stem cells in the absence of feeder cells and in a medium containing 1) a TGFβ family signal transduction pathway inhibiting substance and/or a Sonic hedgehog signal transduction pathway activating substance, and 2) a factor for maintaining undifferentiated state, (2) a second step of culturing the cells obtained in the first step in suspension to form a cell aggregate, and (3) a third step of culturing the aggregate obtained in the second step in suspension in the presence or absence of a differentiation-inducing factor to obtain an aggregate containing neural cells or a neural tissue.

The present invention provides a method for producing retinal cells or a retinal tissue, comprising the following steps (1)-(3): (1) a first step of culturing human pluripotent stem cells in the absence of feeder cells and in a medium comprising a factor for maintaining undifferentiated state, (2) a second step of culturing the pluripotent stem cells obtained in the first step in suspension in the presence of a Sonic hedgehog signal transduction pathway activating substance to form a cell aggregate, and (3) a third step of culturing the aggregate obtained in the second step in suspension in the presence of a 1) a BMP signal transduction pathway activating substance to obtain an aggregate containing retinal cells or a retinal tissue.

A method for producing induced photoreceptor cells from an initial cell is provided, the method includes providing one or more transcription factors (TFs) including at least GON4L to the initial cell. In some versions, the initial cell is a human induced pluripotent stem cell (iPSC). In other embodiments the method includes providing the TFs OTX2 and/or NEUROD1 to the initial cell. Cells produced and obtainable by the method are also provided, the use of these cells as a medicament in the treatment of retinopathy, vectors for inducing the photoreceptor cells and combinations of transcription factors intended for this use.