Abstract: The present invention provides a method for preparing a somatic chimera by using a pluripotent cell genetically engineered not to differentiate into a predetermined type of cell. The present invention particularly provides a method for preventing a pluripotent cell from contributing to the brain and gonad in a somatic chimera animal.

Abstract: The present invention has found that chimeric animals suffer from noticeable inflammation after birth, though neither immune response nor inflammation in the fetal period of these animals has been reported hitherto. This is an unexpected finding since chimeric animals in the fetal period were exclusively analyzed in prior studies and thus it is deemed that immunotolerance has been theoretically established therein. The present invention provides a composition for suppressing immune response or inflammation in the fetal period of a born chimeric animal.

Abstract: The present invention provides a method for producing a chimeric animal using a primed pluripotent stem cell, a tissue stem cell, a progenitor cell, a somatic cell, or a germ cell. The method for producing a chimeric animal according to the present invention comprises introducing a mammal-derived cell into the embryo of a mammal, the cell being primed pluripotent stem cell, tissue stem cell, progenitor cell, somatic cell, or germ cell.

Abstract: Methods of generating functional human organs and tissue in animal bodies suitable for transplantation into human subjects are provided. In particular, the contribution of human donor cells to tissues and organs can be increased in interspecies host embryos by knocking out a growth factor receptor gene such as the insulin-like growth factor 1 receptor or insulin receptor gene. Almost entirely donor-derived functional organs and tissue can be generated by using this method. The methods described herein are useful for generating human organs and tissue in animals and may be helpful for overcoming the current problems with organ shortage for transplantation therapy. Additionally, such organs and tissue can be used in drug discovery, drug screening, and toxicology testing.

Abstract: Cytotoxic T cells derived from human T cell-derived iPS cells may avoid an NK cell missing-self response and may be used for allogeneic administration while maintaining a strong antitumor effect of antigen-specific CTLs. A method may produce a cytotoxic T cell derived from a human T cell-derived iPS cell expressing HLA class I of HLA-restricted class I of an antigen epitope of a CTL and HLA-E. Such a method may include: knocking out all HLA class I of the human T cell-derived iPS cell; introducing a gene of the HLA-restricted HLA class I of the antigen epitope of the CTL and a gene of the HLA-E into the T-iPS cell in which all HLA class I have been knocked out; and redifferentiating the genetically introduced T-iPS cell into a CD8 single-positive T cell.

Abstract: Serum albumin-free media comprising polyvinyl alcohol (PVA) and methods of culturing immune cells in such media are disclosed. The PVA is used as a replacement for fetal bovine serum, bovine serum albumin, and recombinant serum albumin in media. Advantages of using PVA include that it is a chemically-defined reagent that is available at high-purity with minimal batch-to-batch variability.

Abstract: An object of the present invention is to produce a mammalian organ having a complicated cellular composition composed of multiple kinds of cells, such as kidney, pancreas, thymus and hair, in the living body of a non-human animal. The inventors of the present invention applied the chimeric animal assay described above, to a novel solid organ production method. More specifically, the inventors has shown that a model mouse which is deficient of kidney, pancreas, thymus or hair due to the dysfunction of the metanephric mesenchyme that is differentiated into most of an adult kidney, is rescued by blastocyst complementation by the chimeric animal assay, and whereby a kidney, a pancreas, thymus or hair can be newly produced.

Abstract: The present invention discloses a composition of an albumin-free, serum-free medium suited for culturing human hematopoietic stem cells and an albumin-free culturing method. According to the present invention, a method of culturing human hematopoietic stem cells is provided which comprises bringing human hematopoietic stem cells into contact with PVA and a PI3K activator.

Abstract: The present invention discloses a novel means capable of producing a blood chimeric animal in which a state of retaining blood cells originating in a heterologous animal at a high percentage is sustained for a long period of time. The method for producing a non-human animal that retains blood cells originating in a heterologous animal, according to the present invention, comprises transplanting hematopoietic cells of a heterologous animal into a non-human animal, in which hematopoietic cells the function of a gene that acts on the hematopoietic system is modified, The gene that acts on the hematopoietic system is, for example, Lnk gene, When a medium to large mammal is used as a recipient, the survival rate of hematopoietic cells originating in a heterologous animal is dramatically increased such that blood chimerism of 10% or more can be maintained even in a 16 month old animal.

Abstract: A nutrition formulation, which is substantially free of at least one of valine and methionine and which is capable of parenteral or enteral administration. The nutrition formulation supplies sufficient nutrients to sustain life for at least three weeks by successive administration. A composition containing the nutrition formulation can be used for treating adult cell leukemia/lymphoma.

Abstract: It is revealed that an organ such as pancreas can be regenerated by utilizing a fact that the deficiency of an organ is complemented by injecting an induced pluripotent stem cell (iPS cell) into a developed blastocyst in a blastocyst complementation method. Thus, the present invention has solved the above-described object. This provides a method for producing a target organ, using an iPS cell, in a living body of a non-human mammal having an abnormality associated with a lack of development of the target organ in a development stage, the target organ produced being derived from a different individual mammal that is an individual different from the non-human mammal.

Abstract: Compositions, methods, and kits are provided for producing rejuvenated cytotoxic T cells (CTLs) specific for mutated neo-antigen epitopes expressed on cancerous cells, including epidermal growth factor receptor (EGFR) and KRAS neo-antigen epitopes. Antigenspecific CTLs are rejuvenated by reprogramming them into induced pluripotent stem cells (IPSCs) using Yamanaka factors and redifferentiating them back into CTLs while expanding their numbers. After redifferentiation, the IPSC-derived rejuvenated CTLs retain the antigen specificity of the original CTLs from which they were derived, but have the advantage of having longer telomeres and higher proliferative activity than the original CTLs. Pharmaceutical compositions comprising such IPSC-derived rejuvenated CTLs are useful for treating cancers expressing the mutated neo-antigen epitopes recognized by the original CTLs.

Abstract: Provided is an immune cell therapy which uses an iPS technology allowing long-term survival in a living body and which exhibits an excellent antitumor effect by recognition of two antigens. An iPS cell derived from an antigen-specific cytotoxic T cell having a chimeric antigen receptor introduced therein.

Abstract: According to the present invention, there are provided a method for producing a human T cell, which comprises the steps of inducing an iPS cell from a human T cell, and differentiating the iPS cell into a T cell; a pharmaceutical composition comprising the T cell produced by the method; and a method for cell-based immunotherapy using the method.

Abstract: The present invention provides a method for producing a chimeric animal using a primed pluripotent stem cell, a tissue stem cell, a progenitor cell, a somatic cell, or a germ cell. The method for producing a chimeric animal according to the present invention comprises introducing a mammal-derived cell into the embryo of a mammal, the cell being primed pluripotent stem cell, tissue stem cell, progenitor cell, somatic cell, or germ cell.

Abstract: The present invention provides a method for preparing a somatic chimera by using a pluripotent cell genetically engineered not to differentiate into a predetermined type of cell. The present invention particularly provides a method for preventing a pluripotent cell from contributing to the brain and gonad in a somatic chimera animal.

Abstract: According to the present invention, there are provided a method for producing a human T cell, which comprises the steps of inducing an iPS cell from a human T cell, and differentiating the iPS cell into a T cell; a pharmaceutical composition comprising the T cell produced by the method; and a method for cell-based immunotherapy using the method.

Abstract: [Problem to be Solved] The present invention provides a method for producing a chimeric animal using a primed pluripotent stem cell, a tissue stem cell, a progenitor cell, a somatic cell, or a germ cell. [Solution] The method for producing a chimeric animal according to the present invention comprises introducing a mammal-derived cell into the embryo of a mammal, the cell being primed pluripotent stem cell, tissue stem cell, progenitor cell, somatic cell, or germ cell.

Abstract: The present invention has found that chimeric animals suffer from noticeable inflammation after birth, though neither immune response nor inflammation in the fetal period of these animals has been reported hitherto. This is an unexpected finding since chimeric animals in the fetal period were exclusively analyzed in prior studies and thus it is deemed that immunotolerance has been theoretically established therein. The present invention provides a composition for suppressing immune response or inflammation in the fetal period of a born chimeric animal.

Abstract: An object of the present invention is to provide a method of promoting polyploidization of megakaryocytes and thereby producing highly polyploidized megakaryocytes, a method of efficiently producing platelets from polyploidized megakaryocytes, and the like. The present invention provides a method of producing polyploidized megakaryocytes comprising a step of forcing expression of an apoptosis suppressor gene in megakaryocytes before polyploidization and culturing the resulting cells.