The present invention relates, in part, to cell-based gene therapies, including those targeting, by way of non-limiting example, TDP43 and Aβ aggregates, for the use in neurodegenerative disorders, including without limitation Amyotrophic Lateral Sclerosis (ALS) and Alzheimer's Disease, respectively.

The present disclosure provides, in some embodiments, in vitro brain (miBRAIN) having functional and structural properties of in vivo brain as well as methods of identifying compounds capable of influencing brain function.

The invention relates to a method for improving angiogenic potential of a mesenchymal stem cell (MSC), the method comprising culturing the MSC on a substrate having stiffness of about 1 kPa to 100 kPa and coated with a matrix protein, wherein the MSC has improved angiogenic potential when compared with a MSC cultured under identical conditions except not cultured on a substrate having stiffness of about 1 kPa to 100 kPa and not coated with a matrix protein. The invention also relates to a MSC having angiogenic potential when improved by the method, and to therapeutic use of the improved MSC for treating coronary artery disease (CAD) or peripheral artery disease (PAD) in a subject having CAD or PAD.

Provided herein are methods and systems for bio-printing of three-dimensional organs and organoids. Also provided herein are bio-printed three-dimensional organs and organoids for use in the generation and/or the assessment of immunological products and/or immune responses. Also provided herein are methods and system for bio-printing three-dimensional matrices.

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.

A microfluidic device comprising a microfluidic network is described. The device comprises a base, a microfluidic channel and a cover, and the base comprises a diaphragm forming at least part of an inner surface of the microfluidic channel. The device finds use in methods for assessing mechanical strain induced in or by cells, such methods also being described.

The present invention relates, in part, to cell-based gene therapies, including those targeting, by way of non-limiting example, TDP43 and Aβ aggregates, for the use in neurodegenerative disorders, including without limitation Amyotrophic Lateral Sclerosis (ALS) and Alzheimer's Disease, respectively.

Described herein are engineered multilayered vascular tubes comprising at least one layer of differentiated adult fibroblasts, at least one layer of differentiated adult smooth muscle cells, wherein any layer further comprises differentiated adult endothelial cells, wherein said tubes have the following features: (a) a ratio of endothelial cells to smooth muscle cells of about 1:99 to about 45:55; (b) the tube is compliant; (c) the internal diameter of the tube is about 6 mm or smaller; (d) the length of the tube is up to about 30 cm; and (e) the thickness of the tube is substantially uniform along a region of the tube; provided that the engineered multilayered vascular tube is free of any pre-formed scaffold. Also described herein are methods of forming said tubes and uses for said tubes including methods for treating patients, comprising providing such a tube into to a patient in need thereof.

A 3D-printed in vitro model biological microenvironment in examples discussed below may have one or more of the following features: (a) a gel matrix 3D-printed scaffold, wherein the gel matrix comprises a chemical composition configured to culture a first type of live cells, (b) a target chemical disposed at one or more locations within the gel matrix, the target chemical forming a chemical depot from which a chemical gradient is created within the gel matrix, (c) a conduit disposed within the gel matrix and defining a lumen comprising a second type of live cells, wherein the conduit is configured to enable at least some of the first type of live cells to migrate through the conduit and facilitate flow of at least: some of the live cells to an outlet of the conduit, or enable introduction of at least one of other cells, Achemical mediators, or drugs into the 3D-printed microenvironment.

Provided herein is a drug delivery device and composition, such as a particle, comprising conditioned medium. Also provided herein is a method of preparing polymeric particles for release of conditioned medium. Further, a tissue growth scaffold comprising particles for release of conditioned medium is provided.