The present invention provides compositions and methods for the culture and maintenance of pluripotent stem cells. More particularly, the present invention provides for compositions and methods for culturing, maintaining, growing and stabilizing primate pluripotent stem cells in a feeder-free defined media further comprising human serum, or a soluble attachment component of the human serum, for promoting cell attachment.

The invention relates to the fields of biochemistry, pharmacy and oncology. The invention particularly relates to the use of novel stem cell markers for the isolation of stem cells. The invention further relates to the obtained stem cells and their use in for example research or treatment, for example, for the preparation of a medicament for the treatment of damaged or diseased tissue. In one of the embodiments, the invention provides a method for obtaining (or isolating) stem cells comprising optionally preparing a cell suspension from a tissue or organ sample, contacting said cell suspension with an Lgr 6 or 5 binding compound, identify the cells bound to said binding compound, and optionally isolating the stem cells from said binding compound. The invention further relates to means suitable for cancer treatment and even more specific for the treatment of cancer by eradicating cancer stem cells.

The invention relates to methods and media for differentiating cells, for example for obtaining enteroendocrine cells, and to uses of the cells and organoids obtained by said methods. The invention also relates to methods for modulating hormone expression in enteroendocrine cells and medical uses relating to such methods.

The present invention relates to a culture media system that is useful for the isolation and epigenetically stable propagation of normal stem cells in culture which are derived from columnar epithelial tissues and cancer stem cells from epithelial cancers. In certain embodiments, the culture system is a feeder-free system.

Provided is a method for preparing functional hepatic (progenitor) cells or functional small intestinal epithelial (progenitor) cells, comprising the step of culturing an isolated cell population comprising hepatic (progenitor) cells or small intestinal epithelial (progenitor) cells in the presence of an antibiotic. Also, provided is a substantially homogeneous isolated cell population comprising functional hepatic progenitor cells, wherein an expression level of CYP3A4 in the functional hepatic progenitor cells is increased by at least 5 times the expression level thereof in a HeaRG.sup.(R) cell line.

The present invention provides compositions and methods for the culture and maintenance of pluripotent stem cells. More particularly, the present invention provides for compositions and methods for culturing, maintaining, growing and stabilizing primate pluripotent stem cells in a feeder-free defined media further comprising human serum, or a soluble attachment component of the human serum, for promoting cell attachment.

Leucine-rich repeat-containing G-protein coupled receptor 5-positive (LGR5.sup.+) intestinal cells are contacted with an inhibitor of exportin 1 (XPO1), thereby producing functionally differentiated intestinal cells. The LGR5.sup.+ cells can also be contacted with a Wnt agonist. The LGR5.sup.+ cells can also be contacted with a Notch inhibitor.

The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

The present invention addresses IBD from the standpoint of mucosal stem cells cloned from defined regions of the gastrointestinal tract. In the case of pediatric Crohn's disease, for example, isolation of those stem cells according to the methods of the present invention reveals a pattern of inflammatory gene expression in stem cells from the terminal ileum and colon that is epigenetically maintained despite months of continuous cultivation in the absence of immune or stromal cells, or of intestinal microbes. Superimposed on this distributed inflammatory phenotype is a differentiation defect that profoundly and specifically alters the mucosal barrier properties of the terminal ileum. The co-existence of diseased and normal stem cells within the same endoscopic biopsies of Crohn's disease patients implicates an epigenetically enforced heterogeneity among mucosal stem cells in the dynamics of this condition.

A material for binding to a cell culturing protein is disclosed. The material contains a bulk-modified elastomer comprising a plurality of fatty acid moieties covalently bound to the elastomer bulk, wherein the carboxylic acid groups of said moieties are available to provide said binding. Also disclosed are a fluidic device module, a cell culturing scaffold, a fluidic device, the method of synthesizing such a material and a drug testing method. With such a material, a (monolithic) fluidic device module may be manufactured in as few as a single step injection molding process.