The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.

A three-dimensional oxygen-generating bioscaffold capable of supplying cells with a continuous, controlled, and steady source of oxygen and methods of using such an oxygengenerating bioscaffold to prevent hypoxia-induced damage to cells following transplantation are disclosed. In particular, a collagen-based cryogel bioscaffold having calcium peroxide (CPO) incorporated into its matrix is provided, wherein the CPO produces oxygen upon exposure to water. The collagen-based cryogel is designed with a plurality of macropores capable of encapsulating therapeutic cells for cellular therapy. Methods of producing oxygen-generating bioscaffolds and tissue grafts comprising therapeutic cells contained in such oxygen-generating bioscaffolds as well as their use in cellular therapy are also disclosed.

Genetically modified cells, tissues, and organs for treating or preventing diseases are disclosed. Also disclosed are methods of making the genetically modified cells and non-human animals.

Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.

Disclosed herein are human trophoblast stem (hTS) cells, differentiated cells thereof, derivatives thereof such as cellular mass, and uses thereof. The isolation of hTS cells can express FGF4, FGFR-2, Oct4, Thy-1, and stage-specific embryonic antigens distributed in different compartments of the cell. The hTS cells are able to derive into specific cell phenotypes of the three primitive embryonic layers, produce chimeric reactions in mice, and retain a normal karyotype and telomere length. In the hTS cells, Oct4 and fgfr-2 expressions can be knockdown by bFGF. The hTS cells could apply to human cell differentiation and for gene and cell-based therapies.

Provided are three-dimensional pancreatic organoids derived from the pancreas of a genetically mutated mouse, a method for producing the three-dimensional pancreatic organoids, the use of the three-dimensional pancreatic organoids for drug effect verification and/or drug screening, and a universally applicable standardized drug effect evaluation method/drug screening method.

Disclosed herein are microneedle devices, kits comprising the microneedle devices, and methods of using the microneedle devices. Specifically, disclosed is a device for transport of a material across a biological barrier of a subject comprising: a plurality of microneedles each having a base end and a tip, with at least one pathway disposed at or between the base end and the tip; a substrate to which the base ends of the microneedles are attached or integrated; and at least one reservoir which is in connection with the base ends of the microneedles array, wherein the reservoir comprises an agent delivery system, wherein the agent delivery system comprises an agent to be transported across the biological barrier, or a means for producing an agent to be transported across the biological barrier, and a means for detecting a physiological signal from the recipient.

Disclosed herein are differentiation methods for producing SC-β cells, as well as methods for screening stem cell-derived cells to measure gene expression. Also disclosed herein are SC-EC cells.

An in vitro method of preparing insulin-producing cell clusters for transplantation into a subject, comprising (a) seeding pancreatic progenitor cells onto a three-dimensional, porous scaffold at a seeding density greater than about 12.5 million cells per cm.sup.3 of scaffold and less than about 150 million cells per cm.sup.3 of scaffold, wherein the scaffold comprises a plurality of pores having an average pore diameter greater than about 225 μm and less than about 550 pm, and (b) culturing the cells on the scaffold for more than about 3 days in culture medium to obtain insulin-producing cell clusters within the pores of the scaffold for transplantation into a subject. In exemplary aspects, the pancreatic progenitor cells are cells derived from pluripotent stem cells.

Disclosed herein are hepato-biliary-pancreatic organoid (“HBPO” or “HBP organoid”) compositions, and methods of making and using hepato-biliary-pancreatic organoid compositions. The disclosed compositions may have two or more functions selected from hepatic tissue function, biliary tissue function, exocrine pancreatic function, and endocrine pancreatic tissue function. Methods of treating individuals using the hepato-biliary-pancreatic organoid compositions is also disclosed.