The invention features cells, islet-like cells, pancreatic islets and organoids (e.g., human islet-like organoids or HILOs), as well as cell cultures and methods that are useful for the rapid and reliable generation of cells and organoids, such as pancreatic islets and organoids, that are sustainable in vivo and that evade immune detection, rejection and autoimmunity. The invention also features methods of treating pancreatic diseases, such as type 2 diabetes, and pancreatic cancer, using the cells, islet-like cells, pancreatic islets and organoids (e.g., HILOs) that are designed to modulate the activity of immune cells that would otherwise react against them.

The present invention relates to an isolated transgenic pig beta cell wherein the PKC and the PKA pathway are constitutively activated; to a transgenic pig islet comprising said transgenic pig beta cell; and to a transgenic pig comprising said transgenic pig beta cell or said transgenic pig islet. Another object of the invention is a device comprising a transgenic pig beta cell or a transgenic pig islet of the invention. The present invention also relates to the use of said transgenic pig beta cell, said transgenic pig islet, or said device for treating a disease, disorder or condition related to the impaired function of endocrine pancreas or of beta cell.

In various aspects and embodiments, the present invention provides methods for preparing innervated tissue. In various embodiments the invention further provides innervated tissue generated using the methods described herein. In various embodiments the inclusion of optogenetically transducible TENGs or Micro-TENNs in the innervated tissue allows the modulation of tissue or organs by using light to stimulate the optogenetically transducible TENGs or Micro-TENNs.

3D cell cultures and devices for 3D cell culture, and methods of use thereof are provided. In some embodiments, the 3D cell culture comprise pancreatic β cells and can be generated in multi-well plates, allowing for high throughput assays on the cell culture.

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 devices for encapsulating biological cells and are suitable to be implanted into a subject. In different aspects of the disclosure, the devices may comprise a plurality of polymer layers. In one aspect, a device comprises a first polymer layer and a second polymer layer. In some cases, the first polymer layer may be a nanoporous polymer layer. In some cases, the second polymer layer may be a macroporous polymer layer. The first and second polymer layers may define a lumen for enclosing a population of cells. In some cases, the device further comprises a third polymer layer. The devices may be used to transplant cells producing therapeutic agents into a subject (e.g., for the treatment of a disease).

Methods and systems for measuring viability and function of islet cells or stem cell-derived beta cells in an implantable device featuring setting the temperature of the cells in the implantable device to a low temperature to reduce metabolic levels of the cells and reduce oxygen requirements of the cells, and measuring oxygen consumption rates. An oxygen sensor at the inlet of the implantable device and an oxygen sensor at the outlet of the implantable device are used to calculate oxygen consumption rates of the cells, which in turn are indicative of viability. The reduction in temperature can also be used for loading cells into the implantable devices to help reduce ischemic and/or physical injury. The present invention may be used with other cell types, e.g. hepatocytes, heart cells, muscle cells, etc.

Devices and methods for transplanting cells in a host body are described. The cell comprises a porous scaffold that allows the ingrowth of vascular and connective tissues, a plug or plug system configured for placement within the porous scaffold, and a seal configured to enclose a proximal opening in the porous scaffold. The device may further comprise a cell delivery device for delivering cells into the porous scaffold. The method of cell transplantation comprises a two step process. The device is incubated in the host body to form a vascularized collagen matrix around a plug positioned within the porous scaffold. The plug is then retracted from the porous scaffold, and cells are delivered into the vascularized space created within the porous scaffold.

Among the various aspects of the present disclosure is the provision of methods and compositions for the generation of cells of endodermal lineage and beta cells and uses thereof.

A production method for a proliferative liver organoid includes culturing liver stem cells or a tissue fragment including liver stem cells in a growth medium to obtain a proliferative liver organoid, in which the growth medium contains an interleukin-6 family cytokine. A production method for a metabolically activated liver organoid includes culturing the proliferative liver organoid produced by the production method for a proliferative liver organoid in a differentiation medium to obtain a metabolically activated liver organoid, in which the differentiation medium does not substantially contain an interleukin-6 family cytokine.