A genetically modified mesenchymal stem cell including an exogenous nucleic acid including a Klotho encoding region operably linked to a promoter or promoter/enhancer combination, wherein the genetically modified mesenchymal stem cell exhibits increased Klotho expression compared to an unmodified mesenchymal stem cell. Also disclosed are methods of treating a patient including administering a therapeutically effective number of the genetically modified mesenchymal stem cells to the patient. The methods of treatment include treating the patient for a neurodegenerative disease; cancer; organ fibrosis; renal disease; age-related changes of organs or organ systems; to slow, reverse and/or inhibit aging; arteriosclerosis; dementia; diabetes mellitus; erectile dysfunction; autoimmune diseases or autoimmune-related diseases; an inflammatory disease of the lung and sepsis.

Described are cell culture solutions and systems for epithelial stem cell and organoid cultures, formation of epithelial constructs and uses of the same in transplantation.

The present invention generally relates to methods of preparing leukocytes, particularly T cells, ex vivo for use in immunotherapy, particularly cancer immunotherapy. More specifically, the invention relates to methods for the preparation of leukocytes exhibiting cytotoxic properties for use in adoptive cell transfer. The invention also relates to cells and compositions including them for cancer immunotherapy. The invention also relates to methods of immunotherapy, particularly cancer immunotherapy. The present invention relates to a method for producing a leukocyte that has an enhanced capacity for killing a target cell, the method including contacting the leukocyte with a PTPN2 inhibitor in conditions for enabling the inhibitor to inactivate PTPN2 in the leukocyte, thereby producing a leukocyte that has an enhanced capacity for killing a target cell. Preferably, the leukocyte is contacted with the PTPN2 inhibitor in the absence of a T helper cell.

In some aspects, the invention relates to populations of hematopoietic cells that are enriched in PTPσ.sup.− cells and methods of use thereof.

Disclosed are methods of differentiating stem cells in order to obtain hepatocyte-like cells, the method comprising the steps of a) subjecting definitive endoderm to at least one epigenetic modulator to obtain hepatoblasts and b) subjecting the hepatoblasts to at least one stem cell differentiation pathway inhibitor to obtain hepatocyte-like cells; wherein steps a) and b) do not comprise the use of a growth factor. In one preferred embodiment, the epigenetic modulator may be sodium butyrate and/or DMSO and the stem cell differentiation pathway inhibitor may be SB431542 and/or DMSO. Also disclosed are hepatocyte-like cells obtained from the method and uses of these cells such as drug screening.

Provided herein are methods of manufacturing β cells in vitro. Also provided herein are methods of treating a disease in a subject comprising administering the β cells manufactured in vitro to the subject. Also provided herein are methods of differentiating stem cells into β cells.

Provided herein is a method for producing an antibody with improved productivity while maintaining its titer by causing at least one hydroxyamino acid contained in the light chain of the antibody to undergo O-linked glycosylation. Also provided is an antibody so produced.

The present invention provides a method for inducing an inversion of normal blood coagulation factor VIII (F8) gene, a method for correcting an inversion of blood coagulation factor VIII gene in which the inversion has occurred, and a Hemophilia A patient-derived induced pluripotent stem cell in which the inversion is corrected, constructed using the same. The method of the present invention effectively reproduces the inversion of intron 1 and intron 22 of the F8 gene, which is responsible for the majority of severe hemophilia A, and thereby may be effectively used for studying the development mechanism of hemophilia A and as a research tool for screening therapeutic agents. The inversion-corrected induced pluripotent stem cell constructed according the method of the present invention enables an efficient and fundamental treatment for hemophilia A by restoring a genotype in which mutation has occurred to a wild type-like state, without limitation via normal gene or protein delivery.

The present invention provides, in some embodiments, methods of promoting an immune response in a subject in need thereof, comprising administering to the subject a population of immune cells that express an enzyme that facilitates immune cell function in a nutrient-poor environment. The invention also provides, in other embodiments, compositions comprising an ex vivo population of immune cells expressing an enzyme that enhances immune cell function in a nutrient-poor environment.

Provided are a culture medium for expanding and cultivating human liver progenitor cells and an application thereof. The chemical components of the formula of the described culture medium are clear, no serum is present, and various components thereof cooperate with each other to synergize. The culture medium is used for the long-term expansion and cultivation of liver progenitor cells in vitro and is used for maintaining the dryness thereof, is beneficial in quickly and efficiently obtaining a large number of functional liver cells, and is suitable for clinical hepatocyte transplantation application as well as for the use of hepatocyte reactors in bioartificial livers.