Provided herein are methods of using tissue culture plastic-adherent placental adherent cells, e.g. placental stem cells, referred to herein as placental adherent cells, to treat lymphedema and lymphedema-related disorders.

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.

Provided herein is an in vitro model of the blood brain barrier. In some embodiments, the model includes: an endothelial cell layer, and brain tissue layer comprising neuronal cells, and optionally one or more of astrocytes, pericytes, oligodendrocytes, and microglia. In some embodiments, the model further comprises a porous membrane between said endothelial cell layer and the neuronal cell layer. A microfluidic device comprising the same and methods of use thereof are also provided.

An in vitro microfluidic gut-on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and gastrointestinal epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal tissue, e.g., Crohn's disease, colitis and other inflammatory gastrointestinal disorders. These multicellular, layered microfluidic gut-on-chip further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal deuodejeum, small intestinal ileium, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.

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 three-dimensional (3D) tissue constructs and methods of using such 3D tissue constructs to screen for neurotoxic agents. In particular, provided herein are methods of producing and using complex, highly uniform human tissue models comprising physiologically relevant human cells, where the tissue models have the degree of sample uniformity and reproducibility required for use in quantitative high-throughput screening applications.

The presently disclosed subject matter provides systems and methods for producing a three-dimensional model of a human cervix. A microdevice is provided for culturing human cervical cells. The microdevice can include an upper microchannel including live ectocervical epithelial cells. The microdevice can include a lower microchannel including a first parallel lane and a second parallel lane including stromal media. The first and the second parallel lanes can be lined with live vascular endothelial cells. The lower microchannel can include a third parallel lane including uterine fibroblasts and live smooth muscle cells embedded in hydrogel. The first, second, and third lanes of the lower microchannel can be separated by protrusion structures. The third parallel lane can be positioned in the lower microchannel in between the first and the second parallel lanes. The microdevice can further include a porous membrane positioned in between the upper microchannel and the lower microchannel.

The present invention relates to a device which can serve as a model of a hemato-encephalic barrier (HEB) comprising two compartments in which certain cell types are arranged. The invention also relates to the method for preparing said device and the use thereof as a model of the HEB.

The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.

Several embodiments relate to methods of repairing and/or regenerating damaged or diseased tissue comprising administering to the damaged or diseased tissues compositions comprising exosomes. In several embodiments, the exosomes comprise one or more microRNA that result in alterations in gene or protein expression, which in tum result in improved cell or tissue viability and/or function.