The present disclosure provides materials and methods for the delivery of therapeutic nucleic cells (and imaging agents) to tissues.

In one aspect, the present disclosure provides a method for identifying treatment targets relating to tumors. In another aspect, the present disclosure provides a method for identifying biomarkers and molecular features of normal and cancer cells.

Disclosed herein are microfluidic devices that may be used to mimic human organ systems, in particular, pancreatic function, and methods of using same. In particular, disclosed are microfluidic devices that may include a first chamber having a plurality of pancreatic ductal epithelial cells (PDECs), a second chamber having a plurality of pancreatic islets, and a permeable membrane fluidly connecting the chambers. The disclosed devices and methods may be used for the study of pancreatic cell function, for the development of therapeutics, or for the development of personalized therapeutics wherein the cells of the device are obtained from an individual in need of such treatment.

Disclosed are improved compositions and methods for decreasing blood glucagon levels. As disclosed herein, L-glutamine is a selective stimulator of α-cell proliferation generated when glucagon signaling is interrupted. Therefore, disclosed is a method for treating a subject with hyperglucagonemia, e.g., a subject with diabetes, that involves administering to the subject a composition comprising an L-glutamine inhibitor in an amount effective to decrease blood glucagon levels.

The present disclosure is directed to novel methods of treating type-1 or type-2 diabetes by inactivating TLR2 and TLR4 genes together in cells capable of producing insulin and/or regenerating β cells, and providing the cells to a subject in need thereof.

The present invention relates to cells with altered cell cycle control. In particular, the present invention provides cells with altered cell cycle control and uses of such cells to identify metabolically active agents.

This invention relates to the in vitro differentiation of pluripotent cells into pancreatic progenitors by i) culturing pluripotent cells in a definitive endoderm (DE) medium comprising a TGFp ligand, fibroblast growth factor (FGF), bone morphogenetic protein (BMP), a PI3K inhibitor and optionally a GSK3 β inhibitor to produce a population of definitive endoderm cells, ii) culturing the definitive endoderm cells in a first pancreatic medium comprising an activin antagonist; FGF; retinoic acid; and a BMP inhibitor to produce a population of dorsal foregut cells; iii) culturing the dorsal foregut cells in a second pancreatic medium comprising FGF, retinoic acid, a BMP inhibitor, and a hedgehog signalling inhibitor, and; iv) culturing the endoderm cells in a third pancreatic medium comprising FGF. The progenitor cells thus produced may be further differentiated into pancreatic endocrine cells. These methods may be useful, for example, in producing pancreatic cells for therapy or disease modelling.

The present invention provides methods for identifying candidate compounds for limiting development of and/or treating diabetes, and methods for limiting development of and/or treating diabetes.

The present invention provides a method for diagnosing a disease or disorder selected from the group consisting of insulin resistance, a metabolic disorder, diabetes and pre-diabetes in a subject. The method comprises the step of determining the level of a compound represented by structural formula (VI):

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or a salt thereof. Compositions and method of making thereof are also described.

SUSD2 protein is used as a marker in identification, selection or separation of pancreatic internal secretion precursor cells and/or newborn pancreatic internal secretion cells; and a use of an mRNA, for encoding the SUSD2 protein, of a precursor protein as the marker in identification of the pancreatic internal secretion precursor cells and/or the newborn pancreatic internal secretion cells. Analysis of gene expression of pancreatic endoderm cells sourced by induced directional differentiation of human pluripotent stem cells finds the enrichment expression of a SUSD2 gene in the pancreatic internal secretion precursor cells and the newborn pancreatic internal secretion cells. A protein encoded by the SUSD2 gene is a receptor protein on cell membranes. Using the protein as the marker, the identification, the selection or the separation of the pancreatic internal secretion precursor cells and the newborn pancreatic internal secretion cells can be conducted.