The present invention relates to generation of functional beta cells from human pluripotent stem cell-derived endocrine progenitors. The present invention also relates to functional beta cells produced by said methods and uses of said beta cells.

Mononuclear phagocytes derived from induced pluripotent stem cells, denoted as iMPs, which comprise monocytes generated from the induced pluripotent stem cells and optionally further macrophages generated from the induced pluripotent stem cells, are provided for use in improving cognitive function, improving neural health, and/or alleviating or treating a neurodegenerative disorder in a mammal In various embodiments, the iMPs produce macrophages after transplantation or after being stimulated in vitro, and/or express macrophage markers. We showed that iMPs upon administration improve cognition and neural healthy in rodent models of aging, Alzheimer's disease, and amyotrophic lateral sclerosis. Treatment methods are also provided using mononuclear phagocytes generated from autologous stem cells or from induced pluripotent stem cells obtained from autologous cells in patients in need of treatment or prophylaxis of a neurodegenerative disorder.

The present invention relates to an in vitro or ex vivo method for producing a population of pancreatic beta-cells, comprising the step of inhibiting the expression or the activity of Arx in a population of pancreatic alpha-cells. The present invention also relates to method for inducing the conversion of pancreatic alpha-cells in pancreatic beta-cells in a patient in need thereof.

The present invention is directed to methods to differentiate pluripotent stem cells. In particular, the present invention is directed to methods and compositions to differentiate pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage comprising culturing the pluripotent stem cells in medium comprising a sufficient amount of GDF-8 to cause the differentiation of the pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage.

The present invention is directed to methods to differentiate pluripotent stem cells. In particular, the present invention is directed to methods and compositions to differentiate pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage comprising culturing the pluripotent stem cells in medium comprising a sufficient amount of GDF-8 to cause the differentiation of the pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage.

Fully defined media that support pluripotent cell viability, proliferation, cloning, and derivation, as well as methods and compositions including these media are described. Methods for deriving iPS cells from adult individuals under defined, xeno-free conditions are also described.

The present invention is directed to methods to differentiate pluripotent stem cells. In particular, the present invention is directed to methods and compositions to differentiate pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage comprising culturing the pluripotent stem cells in medium comprising a sufficient amount of GDF-8 to cause the differentiation of the pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage.

The present invention is directed to methods to differentiate pluripotent stem cells. In particular, the present invention is directed to methods and compositions to differentiate pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage comprising culturing the pluripotent stem cells in medium comprising a sufficient amount of GDF-8 to cause the differentiation of the pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage.

The present invention relates to a method for inducing proliferation and/or differentiation of hematopoietic stem/progenitor cells, the method comprising activating the y-aminobutyric acid pathway of hematopoietic stem/progenitor cells. The present invention also provides a culture medium for inducing proliferation and/or differentiation of hematopoietic stem/progenitor cells into NK cells and use thereof.

The invention provides an engineered immune cell, wherein the engineered immune cell comprises a gain-of-function mutation in a Cav channel and/or overexpresses an L-type voltage-gated calcium (Cav) channel. Also provided are related engineered immune cells for use in medicine. Also provided are L-type Cav channel agonists for use in a method of stimulating cell killing activity of an immune cell in a subject having a proliferative disorder. Pharmaceutical compositions and methods are also provided.