The present invention concerns methods and compositions for gene therapy, in particular in vivo gene therapy for delivery of bioactive glial derived neurotrophic factor (GDNF) for the treatment of Parkinson's Disease. The invention also concerns mammalian cells capable of producing GDNF in increased amounts as well as the use of these cells for recombinant production of bioactive GDNF and for therapeutic use. The invention also includes a device that may be implanted in the cochlear of a patient that is capable of secreting GDNF.

The present invention relates to a method of patterning and chopping 3D organoids prepared from human pluripotent stem cells, culturing the stem cells or progenitor cells, and inducing the differentiation thereof to obtain a large amount of finally differentiated cells. Compared to cells differentiated by a conventional differentiation method, the cells obtained in a large amount exhibit remarkably superior effects in terms of reproducibility, stability, and functionality, and thus are expected to be very useful for cell therapeutic agents or for the screening of therapeutic drugs.

Compositions and methods for inducing pluripotent stem cells into retinal ganglion cells for administration to a subject for treating progressive optic neuropathies, thereby alleviating symptoms of such disorders including glaucoma.

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

The present invention relates to methods for differentiating stem cells into ventral midbrain dopaminergic progenitor cells, and into mesencephalic dopaminergic neurons, and compositions, kits, and uses thereof.

Provided is a human-derived sensory neuron induction culture system. A combination of a small molecule inhibitor LY2157299 and a growth factor is added into a serum-free basal medium. Compared with an induction method involving serum, not only is the efficiency of inducing pluripotent stem cells into sensory neurons greatly improved, but the expression of a variety of ion channel proteins is also significantly improved, thereby achieving successful induction of multiple induced pluripotent stem cells from different sources into sensory neurons.

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) contacting a cell aggregate including neural cells and having a three-dimensional structure with a preservation solution at 0° C. to 30° C. prior to freezing to prepare a preservation solution-soaked cell aggregate; and (2) cooling the preservation solution-soaked cell aggregate obtained in step (1) from a temperature at least about 5° C. higher than the freezing point of the preservation solution to a temperature about 5° C. lower than the freezing point at an average cooling speed of 2 to 7° C./min to freeze the cell aggregate.

A method of obtaining a pluripotent-like multipotent cell, including providing a cell of a first type which is not a pluripotent-like multipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pluripotent gene regulator in the cell of a first type, to a level at which the at least one pluripotent gene regulator is capable of driving transformation of the cell of a first type into the pluripotent-like multipotent cell; and placing or maintaining the cell in a differentiation medium and maintaining intracellular levels of the at least one pluripotent gene regulator for a sufficient period of time to allow a stable pluripotent-like multipotent cell to be obtained; wherein the pluripotent-like multipotent cell so obtained does not exhibit teratoma formation in vivo.

Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.

Methods for generating in culture of cells resembling mammalian trophectoderm-lineage cells from mammalian pluripotent stem cells are provided, along with the related compositions.