The present invention is primarily directed to provide a new process capable of performing direct conversion of or induction from a somatic cell to brown adipocytes with low molecular weight compounds, without performing artificial gene transfer.

The present invention includes, for example, a process for producing brown adipocytes by direct differentiation induction from somatic cells, comprising a step of culturing a somatic cell in a serum-free differentiation induction medium in the presence of a selective PPARγ agonist and a cAMP inducer.

According to the present invention, direct conversion of or induction from somatic cells to brown adipocytes can be effectively performed without gene transfer. The brown adipocytes obtained by the present invention are useful as regenerative medicine, models of human brown adipocytes and human beige cells, and the like.

Provided herein is a dual cell aggregate culture of retinal epithelial cells and photoreceptors for use as a research tool, such as the screening of compounds or model for study of retinal diseases, as well as a therapeutic for treating ocular diseases.

The present invention relates to the combined use of a neuropilin-1 (Nrp-1) neutralizing agent and of a programmed cell death-1 (PD-1) neutralizing agent for killing cancer cells, typically for treating cancer, as well as to corresponding pharmaceutical compositions and kits, and to corresponding diagnostic and therapeutic methods. The invention further relates to in vitro, ex vivo and in vivo methods for detecting CD8.sup.+ TILs capable of recognizing cancer cells, for predicting the response of a subject to anti-PD-1 treatment of cancer, and for identifying a subject who responds therapeutically to a treatment of cancer with an antibody combination therapy comprising anti-Nrp-1 and anti-PD-1 antibodies.

This invention relates to compositions and methods for the transplantation of GABAergic neurons. GABAergic neurons and compositions comprising the same according to the present invention may be used as cell-based therapies for restoring or reinforcing central inhibition in the nervous system of a subject and for the treatment of neurological conditions, diseases and disorders associated with impaired or aberrant neural function. In a preferred embodiment, the transplant composition comprise of GABAergic neurons, a GFR-alpha agonist, and at least one cell death inhibitor, and that the GABAergic neurons are generated by differentiating pluripotent stem cells, multipotent stem cells, or progenitor cells.

The invention relates inter alia to a method for differentiating a muscle progenitor cell, comprising the step of: culturing a muscle progenitor cell in a serum-free medium for differentiating a muscle progenitor cell, wherein said serum-free medium comprises at least one differentiation inducer selected from the group consisting of a lysophosphatidic acid receptor 1 (LPAR1) agonist, a lysophosphatidic acid receptor 3 (LPAR3) agonist, an oxytocin receptor (OXTR) agonist, a glucagon receptor (GCGR) agonist, a lactate and a Notch signaling pathway inhibitor.

A method of cell culture comprising providing cells in a cell culture medium to start a cell culture process, and, maintaining at least one metabolite selected from 3-(4-hydroxyphenyl)lactate, 4-hydroxyphenylpyruvate, phenyllactate, indolelactate, indolecarboxylic acid, homocysteine, 2-hydroxybutyric acid, isovalerate and formate below a concentration C1 in the cell culture medium, wherein C1 is 3 mM and/or (ii) maintaining at least one amino acid selected from phenylalanine, tyrosine, tryptophan, methionine, leucine, serine, threonine and glycine below a concentration C2 in the cell culture medium, wherein C2 is 2 mM.

A method for producing hepatocytes from hepatoblasts is provided. The method includes the step of culturing the hepatoblasts in a medium containing a compound selected from the group consisting of pregnenolone and an adrenergic agonist. The hepatoblasts can be obtained by culturing endodermal cells in a medium containing DMSO, and the endodermal cells can be obtained by culturing pluripotent stem cells in a medium containing Activin A and a GSK-3 inhibitor. Accordingly, a method for producing hepatocytes from pluripotent stem cells is also provided by employing the method of the present invention.

Provided herein are compositions including compounds and/or cells for treating a disease associated with Group 2 innate lymphoid cells (ILC2s), and methods of treatment.

The present disclosure provides compositions, kits, and methods for promoting in vitro maturation of cells. The present disclosure also provides methods of screening compounds that are suitable for promoting in vitro maturation of cells.

The present disclosure relates to a method for improving the culture conditions of cultures of primary sweat gland cells and/or three-dimensional sweat gland equivalents, where the culture with from about 500 to about 500,000 sweat gland cells and a diameter of from about 100 to about 6,000 nm is initially prepared and then cultivated in a culture medium with neurotransmitters and/or from about 11 to about 100 ng/ml of at least one growth factor. Cultivation of these cells and models in a culture medium containing at least one neurotransmitter and/or from about 11 to about 100 ng/ml of at least one growth factor leads to an increase of sweat-gland-specific marker proteins. As a result, a loss of function, which occurs with an absence of or only low expression of these markers, can be avoided.