The present invention relates to the use of the biomarker Flattop (Fltp) for distinguishing mature cells from immature progenitor cells. The present invention further relates to a method for distinguishing a mature cell from an immature progenitor cell, the method comprising: determining the presence or absence of the biomarker Flattop (Fltp) in a cell; wherein the presence of Fltp in the cell indicates that the cell is a mature cell and wherein the absence of Fltp in the cell indicates that the cell is an immature progenitor cell. Furthermore, the present invention relates to a method of identifying a compound suitable for differentiating immature progenitor cells into mature cells as well as to a method of identifying a compound suitable for preventing the de-differentiating of mature cells.

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.

The present invention provides for methods of differentiating induced pluripotent stem cells into pancreatic progenitor cells, pancreatic ductal cells, pancreatic endocrine cells, pancreatic acinar cells, and pancreatic organoids. Cells created by these methods are also provided. Further provided are disease models and methods of drug screening.

Provided are a three-dimensional pancreatic organoid derived from the pancreas of a genetically modified mouse, a method for fabricating the three-dimensional pancreatic organoid, and use of the three-dimensional pancreatic organoid for drug effect verification and/or drug screening.

Disclosed herein are methods for generating SC- cells, and isolated populations of SC- cells for use in various applications, such as cell therapy.

A method for producing immunoprotected pancreatic islets including forming double-layer PEGylated pancreatic islets by adding a first heterobifunctional polyethylene glycol (PEG) molecule and a second heterobifunctional PEG molecule to pancreatic islets and forming immunoprotected pancreatic islets by conjugating a plurality of JAG-1 peptides to the double-layer PEGylated pancreatic islets.

This document provides materials and methods for making and using functional (e.g., vascularized) organ models (e.g., pancreas models). For example, functional pancreas models including an ECM containing a plurality (e.g., two or more) of pancreatic islets, and a vascular network are provided.

It is an object of the present invention to provide a method for efficiently directing differentiation into insulin-producing cells in a xeno-free culture system. According to the present invention, there is provided a method for directed differentiation into insulin-producing cells, comprising culturing stem cells in the following steps (1) to (5): (1) a step of culturing stem cells in a medium comprising an activator of activin receptor-like kinase-4/-7 and a GSK3 inhibitor and then culturing in a medium comprising an activator of activin receptor-like kinase-4/-7; (2) a step of culturing the cells obtained in step (1) in a medium comprising a hedgehog signaling inhibitor and an FGF; (3) a step of culturing the cells obtained in step (2) in a medium comprising a retinoic acid receptor agonist, a hedgehog signaling inhibitor and a BMP signaling inhibitor; (4) a step of culturing the cells obtained in step (3) in a medium comprising a TGF- type I activin receptor-like kinase-4/-5/-7 inhibitor and a BMP signaling inhibitor; and (5) a step of culturing the cells obtained in step (4) in a medium comprising a phosphodiesterase inhibitor.

In one embodiment, the invention provides a method of regenerating organs and tissues in a subject suffering from one or more organ or tissue manifestations of glucose supply side associated metabolic syndrome, the method comprising: (a) confirming that the subject suffers from or is at risk for suffering from organ and/or tissue damage associated with a glucose supply side associated metabolic syndrome; and (b) co-administering to the subject an effective amount of a pharmaceutical composition comprising a first and optionally a second active composition, said first active composition comprising an ileal brake hormone releasing substance encapsulated within an enteric coating which releases said substance within said subject's ileum and ascending colon causing release of at least one ileal brake hormone from L-cells of said subject, said optional second active composition being formulated in immediate and/or early release form in an over coating onto said enteric coating, wherein said second composition is beneficial to at least one aspect of said subject's metabolic syndrome manifestations. Coadministration methods with a second pharmaceutical composition are also disclosed.

Methods are provided for obtaining a sample of cells from an isolated donor pancreas or isolated pancreatic islets and analyzing the sample using flow cytometry to determine the percentage of cells in the sample that express detectable levels of ALDH1 A3. If the percentage of ALDH1 A3-expressing cells in the sample is about 3% or lower, then it is possible to determine that the pancreas or islets are healthy enough for implantation into a subject, and implanting the pancreas or islets. If the percentage of ALDH1 A3-expressing cells is above about 5%, then it is determined that the pancreas or islets are not suitable for implantation into the subject and discarding the pancreas or islets. Isolated non-insulin-producing or low-insulin-producing pancreatic beta cells are also provided.