Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic endocrine cells. In some aspects, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.

[Problem] An object of the present invention is to produce cancer cell clusters with intrinsic biological properties as cancer tissues, such as morphological polarity and tissue motion polarity, in vitro. [Solution] The present invention relates to a cell culture substrate including a base material and a biocompatible polymer layer, the substrate including a plurality of rough sections on the surface of the substrate, wherein the rough sections are not covered with the biocompatible polymer layer, have a predetermined surface structure with a predetermined shape, and are disposed at predetermined intervals. With the present invention, it is possible to obtain a live cancer cell aggregate having morphological polarity and tissue motion polarity similar to that observed in vivo, by a very easy operation of culturing cancer cells on a cell culture substrate having a predetermined structure, thereby performing live imaging of microtumors in vitro is enabled, which has been conventionally impossible. Moreover, since such a cancer cell aggregate is considered to reproduce a series of flow of development, proliferation, infiltration, metastasis, and recurrence of cancer in vivo, the cancer cell aggregate can be utilized as a research tool in cancer research, or for screening for an anticancer drug.

Methods of using pulsed focused ultrasound (pFUS) therapy to treat pancreatic disorders such as type 1 diabetes, pancreatitis, and pancreatic cancer are provided. The methods utilize pulsed focused ultrasound (pFUS) therapy either by itself or in combination with islet transplantation and/or stem cell therapy to promote regeneration of damaged pancreatic tissue, increase insulin secretion in response to glucose, or improve engraftment and revascularization of transplanted islets or beta cells. Additionally, methods of using pFUS are provided for modulating paracrine secretion in the pancreas, islets, beta cells, or stem cells, or at a transplantation site to therapeutically alter levels of various factors including, without limitation, cytokines, growth factors, angiogenic factors, and cell adhesion molecules.

The disclosure relates to stem cells and their therapeutic use in the treatment and/or prevention of pancreatic diseases or disorders. Provided herein are compositions comprising c-kit positive pancreatic stem cells and methods of preparing and using c-kit positive pancreatic stem cells for the treatment and/or prevention of pancreatic diseases or disorders.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Methods for cryopreservation of biological samples are provided. The biological samples are sub-millimeter or millimeter scale biological materials. The biological samples are pancreatic islets and stem cell derived islets. Methods for cryopreservation of islets using cryomesh and multi-step loading and unloading of CPA cocktails are provided. Methods disclosed result in vitrified and rewarmed islets with high recovery, viability and functionality. Methods are scalable for high throughput production of large amounts of vitrified and rewarmed islets for use in therapeutic transplantation.

The present invention provides devices and methods for delivering a population of cells or a therapeutic agent to a subject in need thereof.

The present disclosure provides methods and compositions for generating populations of auxotrophic cells and populations of differentiated cells and selecting populations of transfected cells using split auxotrophy.

The present invention relates to a method for preparing commercial scale quantities of canine functional beta cells and to the establishment of cell lines from immature canine pancreatic tissues. It also relates to a method of diagnosis using canine beta cell tumours or cells derived thereof. The method comprises sub-transplantation procedure to enrich the graft in proliferating beta cells, allowing generating canine Beta cell lines. Such lines express, produce and secrete insulin upon glucose stimulation.

The present invention relates to a method to differentiate pluripotent stem cells to a primitive streak cell population, in a stepwise manner for further maturation to definitive endoderm.