There is described an isolated 3-dimensional liver spheroid wherein said spheroid has: increased ATP content as compared to a 3-dimensional liver spheroid cultured in Complete William's E medium alone; the same or increased activity of cytochrome P450 1A1 and cytochrome P450 1B1 as compared to a 3-dimensional liver spheroid cultured in Complete William's E medium alone; and increased albumin secretion as compared to a 3-dimensional liver spheroid cultured in William's E medium alone.

The present invention is related to 6-6 Fused Bicyclic Heteroaryl Compounds of the Formula A2 or A1 and their Use as LATS Inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; wherein the variables are as defined herein.

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The present invention further relates to a method of LATS inhibition in a cell population using a compound of Formula A1, or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, their use in the treatment and management of diseases or disorders.

Disclosed are living, three-dimensional tissue constructs for in vitro scientific and medical research, arrays thereof, and methods of making said tissues and arrays.

Provided herein are artificial lung organoids. The artificial lung organoids may include an epithelial cell layer comprising mammalian lung epithelial cells, a stromal cell layer comprising mammalian lung fibroblast cells and an endothelial cell layer comprising mammalian endothelial cells. The artificial lung organoids may optionally include a porous membrane between said epithelial cell layer and said stromal cell layer and/or between said stromal cell layer and said endothelial lung cell layer.

An in vitro microfluidic organ-on-chip device is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a stem cell-based Lung-on-Chip is described. This in vitro microfluidic system can be used for modeling differentiation of cells on-chip into lung cells, e.g., a lung (Lung-On-Chip), bronchial (Airway-On-Chip; small-Airway-On-Chip), alveolar sac (Alveolar-On-Chip), etc., for use in modeling disease states of derived tissue, i.e. as healthy, pre-disease and diseased tissues. Additionally, stem cells under differentiation protocols for deriving (producing) differentiated lung cells off-chips may be seeded onto microfluidic devices at any desired point during the in vitro differentiation pathway for further differentiation on-chip or placed on-chip before, during or after terminal differentiation.

A composition including adult pluripotent olfactory stem cells is provided. The adult pluripotent olfactory stem cells are obtained by culturing a cell mixture from an olfactory tissue of a mammal in media containing growth factors and then isolating cells which express B-lymphoma moloney murine leukemia virus insertion region-1 (Bmi-1).

Disclosed is a method of producing vascularized respiratory (airway and alveolar) organoids using blood vessel organoids. More particularly, vascularized respiratory (airway and alveolar) organoids with a vascular network are produced by fusing respiratory (airway and alveolar) organoids with blood vessel organoids to induce vascularization. The vascularized respiratory (airway and alveolar) organoids can have functions very similar to the human respiratory whole region, so they are expected to be transplanted into humans to treat respiratory related diseases or be used as an in vitro respiratory whole region model.

Methods are provided for production of differentiated tissue equivalent model systems from cryopreserved undifferentiated cells. The methods include seeding undifferentiated cells directly onto a support for differentiation immediately after recovery from cryopreservation, without intervening steps for expansion, harvesting, counting, or dilution of the cells.

A method for producing continuously replicating, non-transformed pig macrophages, comprising culturing a cell preparation from an organ obtained from a pig in culture medium to which GM-CSF has been added thereby differentiating the cell population into self-renewing, non-transformed macrophages.

A method for vascular regeneration comprises delivering endothelial cells to a lung scaffold, delivering perivascular cells to the lung scaffold, and providing a multiphase culture program to the scaffold. The multiphase culture program comprises a first phase including delivering an angiogenic medium, e.g., having 40-100 ng/ml of pro-angiogenic factors, and a second phase including delivering a stabilization medium, e.g., having 0.5-2% of serum and 1-20 ng/ml of angiogenic factors.