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.

The present invention relates to a method of converting human fibroblasts into neural stem cells, and more particularly, to a method of directly converting human fibroblasts into neural stem cells using only a combination of small-molecule compounds without any introduction of a foreign gene, and to the use of the neural stem cells. The method of directly converting human fibroblasts into neural stem cells using only small-molecule compounds without any introduction of a foreign gene makes it possible to obtain genetically stable neural stem cells in an amount sufficient for use in cell therapy by deriving them from human fibroblasts. The neural stem cells obtained according to the method of the present invention can differentiate into functional neural cells and are not tumorigenic. Thus, these neural stem cells are useful as cellular therapeutic agents for treatment of brain diseases.

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.

A process of using a fish plasma component in a nutrient medium for cell culture includes obtaining a fish that is a progeny of domesticated broodstock that are reared under consistent and reproducible conditions. Blood is obtained from the fish, and plasma is separated from the blood. One or more specific components of the plasma are then extracted, and cells are cultured in a nutrient medium using the one or more extracted plasma components, and none of any remainder of the plasma. The plasma and/or the plasma components is/are tested for presence and/or level of endotoxin. Extracting the one or more specific components of the plasma, and/or culturing the cells is only performed if the testing indicates an endotoxin level below a predetermined threshold. The cells cultured using the extracted one or more plasma components are other than fish cells.

A method of treating a mammal with one of a central nervous system injury and a neurodegenerative disorder comprising isolating, culturing, and generating neural progenitor cells from a mammalian placenta, and transplanting the placenta derived neural progenitor cells into a brain of the mammal.

Methods for generating human committed midbrain neural stem cells (NSCs) and midbrain neural progenitor cells (midbrain NPCs) from human pluripotent stem cells are provided using chemically-defined culture media that allow for generation of the midbrain NPCs in as little as six days. The midbrain NPCs can be further differentiated to mature dopaminergic neurons. Culture media, isolated cell populations and kits are also provided.

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.

This invention relates to genetic engineering, in particular to an insertion site for a transgene, cells comprising a transgene or other modification at that insertion site, vectors for targeting that insertion site, and methods for creating transgenic cells by insertion or other modification at that site. The insertion site, or “safe harbour locus”, is identified within the SPATA13 gene on human chromosome 13q12.12. Mammalian cells comprising a genetic modification within the SPATA13 gene on chromosome 13q12.12 are described, wherein the modification may be an insertion such as an integrated transgene. Nucleic acid molecules able and adapted to guide the insertion of a transgene to that insertion site are also described. These cells or nucleic acids may be useful in therapy.

A method for rejuvenating glial progenitor cells and rejuvenated glial progenitor cells rejuvenated by such method are disclosed. The method comprises introducing a population of genetically modified glial progenitor cells into the brain and/or brain stem of a subject, wherein the genetically modified glial progenitor cells have increased expression of one or more genes compared to the same type of glial progenitor cells that have not been genetically modified, and wherein the one or more genes are selected from the group consisting of ARX, CEBPZ, DLX1, DLX2, ELK1, ETS1, ETV4, KLF16, MYBL2, MYC, NFYB, POU3F1, SMAD1, SOX3, SP5, TCF12, TFDP1, TP53, ZIC3 and ZNF195.

Methods and compositions for modifying glycans (e.g., glycans expressed on the surface of live cells or cell particles) are provided herein.