Abstract: The present invention relates to a method for inducing the differentiation of corneal epithelial cells from pluripotent stem cells. More specifically, the present invention relates to a method for autonomously differentiating pluripotent stem cells, such as human iPS cells, into ectodermal cell lineage in a serum-free medium without using feeder cells and inducing the differentiation of the resultant ocular surface ectodermal lineage cells into corneal epithelial cells.

Abstract: The present invention relates to three-dimensional (3D) tissue constructs and methods of using such 3D tissue constructs to screen for neurotoxic agents. In particular, provided herein are methods of producing and using complex, highly uniform human tissue models comprising physiologically relevant human cells, where the tissue models have the degree of sample uniformity and reproducibility required for use in quantitative high-throughput screening applications.

Abstract: The present invention provides apparatus and methods for production of tissue structures and organs. In some examples, a cleanspace facility may be equipped with modelling hardware and software, nanotechnology and microelectronic apparatus, and additive manufacturing equipment to print cells and support matrix to allow cells to grow into tissue structures and organs. Various methods relating to using and producing the tissue engineering system are discussed.

Abstract: This invention relates to a transgenic non-human mammal whose genome comprises a polynucleotide sequence encoding a T cell receptor that is specific to a fluorescent protein, where the T cell of the non-human mammal comprises the T cell receptor. The present invention also relates to an isolated T cell from the transgenic non-human mammal of the present invention, an isolated T cell comprising an expression construct comprising a polynucleotide sequence that encodes a T cell receptor that is specific to a fluorescent protein, methods of making transgenic non-human mammals comprising T cell receptors that are specific to a fluorescent protein, a method of depleting cells in a non-human mammal using isolated T cells that encode a T cell receptor that is specific to a target protein, and a method of characterizing a T cell response to an agent.

Abstract: Disclosed herein is a recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein; and a 3?UTR nucleic acid sequence. Also disclosed is a pharmaceutical composition comprising the recombinant nucleic acid and a method of treating Leber's hereditary optic neuropathy (LHON) using the pharmaceutical composition.

Abstract: Provided herein are methods of preparing a poloxamer for use in a cell culture medium. Also provided herein are cell culture media containing the poloxamer prepared by the methods herein, as well as methods of using the media for cell culturing and polypeptide production from cells.

Abstract: Factor VIII variants and methods of use thereof are disclosed. In particular embodiments, Factor VIII variants are expressed more efficiently by cells over wild-type Factor VIII proteins, are secreted at increased levels by cells over wild-type Factor VIII proteins, exhibit enhanced activity over wild-type Factor VIII proteins and are packaged more efficiently into viral vectors.

Abstract: Disclosed herein are methods of generating induced pluripotent stem cells. The method involves providing a quantity of somatic or non-embryonic cells, contacting the contacting the somatic or non-embryonic cells with a quantity of one or more reprogramming factors and one or more RNA molecules, and culturing the somatic or non-embryonic cells for a period of time sufficient to generate at least one induced pluripotent stem cell. Various reprogramming factors and RNA molecules for use in the methods are disclosed herein. Also disclosed are cell lines and pharmaceutical compositions generated by use of the methods.

Abstract: Provided herein are methods and compositions for dynamically controlling and targeting multiple immunosuppressive mechanisms in cancer. Some aspects provide cells engineered to produce multiple effector molecules, each of which modulates a different immunosuppressive mechanisms of a tumor, as well as methods of using the cells to treat cancer, such as ovarian, breast, or colon cancer.

Abstract: An object of the present invention is to provide a novel medical application to regenerative medicine that uses pluripotent stem cells (Muse cells). The present invention provides a cell preparation for treating cerebral infarction and sequelae associated therewith that contains SSEA-3-positive pluripotent stem cells isolated from mesenchymal tissue in the body or cultured mesenchymal cells. The cell preparation of the present invention is based on a brain tissue regeneration mechanism by which Muse cells differentiate into nerve cells and the like in damaged brain tissue by administering Muse cells into cerebral parenchyma.

Abstract: The invention provides a method of producing a synthetic retina, comprising: i) providing a three dimensional stem cell culture throughout the differentiation time course, ii) differentiating the three dimensional stem cell culture for a first time period in a first neural cell culture medium comprising: a) L-glutamine; b) B27 supplement; and c) an IGF-1 receptor agonist, iii) subsequently differentiating the three dimensional stem cell culture for a second time period in a second neural cell culture medium comprising: a) L-glutamine; b) B27 supplement; c) N2 supplement; and d) an IGF-1 receptor agonist, wherein said synthetic retina contains laminated retinal tissue comprising.

Abstract: The invention provides a method for producing a retinal tissue by (1) subjecting pluripotent stem cells to floating culture in a serum-free medium containing a substance inhibiting the Wnt signal pathway to form an aggregate of pluripotent stem cells, (2) subjecting the aggregate to floating culture in a serum-free medium containing a basement membrane preparation, and then (3) subjecting the aggregate to floating culture in a serum-containing medium. The invention also provides a method for producing an optic-cup-like structure, a method for producing a retinal pigment epithelium, and a method for producing a retinal layer-specific neural cell.

Abstract: The invention provides in certain embodiments, a method of generating a re-programmed differentiated epithelial cell comprising (a) contacting a non-stem somatic cell obtained from a subject with an effective amount of a de-differentiation agent to form a de-differentiated cell, and (b) transfecting the de-differentiated cell with an expression cassette comprising a promoter operably linked to a nucleic acid encoding a conversion agent to form a re-programmed differentiated cell. The invention also provides in certain embodiments, a method of generating a re-programmed differentiated epithelial cell comprising (a) contacting a non-stem somatic cell obtained from a subject with an effective amount of a de-differentiation agent to form a de-differentiated cell, and (b) contacting the de-differentiated cell with a conversion agent to form a re-programmed differentiated cell.

Abstract: Disclosed herein are methods and compositions for modifying TCR genes, using nucleases (zinc finger nucleases or TAL nucleases) to modify TCR genes.

Abstract: The invention generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency. In particular embodiments the invention is predicated upon increased expression of an estrogen related receptor and changes in the oxidative and glycolytic pathways.

Abstract: The purpose of the present invention is to provide a method of purification and preparation of cultured corneal endothelial cells, and in particular, to provide cell surface markers for use in corneal endothelial cells not including transformed cells. Provided are cell markers for distinguishing normal cells and transformed cells, in particular normal and transformed corneal endothelium cells. These cell markers relate to specific cell surface markers, for example, to a normal corneal endothelial surface marker such as CD166, and a transformed cell surface marker such as CD73. By using the transformed cell surface marker such as CD73 to remove transformed cells by sorting, it becomes possible to improve purity of a normal cultured corneal endothelium. By using normal corneal endothelial surface marker such as CD166, or by combined use with the transformed cell surface marker, it becomes possible to provide a means for verifying the purity of a prepared corneal endothelium.

Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Abstract: A three dimensional tissue printing method is disclosed. The three dimensional tissue printing method includes the following steps: performing large support stand printing to form a first printing body; performing small support stand printing to form second printing body on the first printing body and forming a tissue structure by crossly connecting in between the first printing body and the second printing body. Besides, a three dimensional tissue printing device and artificial skin are also presented.

Abstract: The invention is directed to methods of inducing cell recruitment and tissue regeneration at a target site in a subject. It is also based, in part, on the discovery that a subject's own biologic resources and environmental conditions can be used for in situ tissue regeneration and thereby reduce or eliminate the need for donor cell procurement and ex vivo manipulation of such donor cells. Methods are disclosed for recruitment of a subject's own stem cells to a target region by inducing a sustained positive pressure at a target site, such as the kidney, thereby increasing the number of pluripotent cells capable of differentiating to regenerate the target tissue.