Steam cell and exosome compositions via combination therapy, related gene therapy and pluripotent stem cell derived muscle regeneration as having therapeutic utility to treat a variety of diseases and disorders, e.g., cardiovascular disease, Duchenne muscular dystrophy, and fibrotic disease.

An immortalized sweat gland myoepithelial cell which expresses -SMA and pan-cytokeratin and has a sphere forming ability after subculture at least 5 times. A method for producing immortalized sweat gland myoepithelial said method comprising: while culturing a cell structure, wherein sweat gland myoepithelial cells are exposed on a surface, in a state of being suspended in a medium, transferring an immortalizing gene into the cells; and then culturing the transgenic structure thus obtained in a state of being suspended in the medium to thereby obtain immortalized sweat gland myoepithelial cells.

An immortalized sweat gland myoepithelial cell which expresses -SMA and pan-cytokeratin and has a sphere forming ability after subculture at least 5 times. A method for producing immortalized sweat gland myoepithelial said method comprising: while culturing a cell structure, wherein sweat gland myoepithelial cells are exposed on a surface, in a state of being suspended in a medium, transferring an immortalizing gene into the cells; and then culturing the transgenic structure thus obtained in a state of being suspended in the medium to thereby obtain immortalized sweat gland myoepithelial cells.

Methods of using a small molecule MYH11 agonist to inhibit intimal hyperplasia and to maintain a contractile phenotype in vitro and in vivo are described. Also described herein are methods for generating human contractile smooth muscle cells from human pluripotent stem cells under defined conditions in the presence of the small molecule MYH11 agonist.

The present invention provides a method for producing a heart organoid and/or a lung organoid, comprising the step of: culturing an embryoid body in the presence of an FGF protein on a surface of a gel containing an extracellular matrix constituent protein.

A method for analyzing a test agent to determine whether or not the test agent affects electrical activity of a cardiomyocyte is disclosed. The method includes: i) providing an induced pluripotent stem cell (iPSC) derived cardiomyocyte (iPSC-DM) that has been modified to contain an oligonucleotide that increases iPSC-DM I.sub.Kr; ii) measuring I.sub.Kr and action potential of the iPSC-DM of i); subsequently iii) contacting the iPSC-DM of i) with the test agent; and iv) measuring I.sub.Kr and action potential of the iPSC-DM that has been contacted with the test agent; and determining a difference between the I.sub.Kr and action potential of ii) and the I.sub.Kr and the action potential of iv) to indicate the test agent affects the electrical activity of the cardiomyocyte, or determining the same I.sub.Kr and action potential of ii) and iv) to indicate the test agent does not adversely affect the electrical activity of the cardiomyocyte.

The microfluidic chip can comprise at least one multichamber flow assembly that can comprise a plurality of microchannels. The plurality of microchannels can comprise a first microchannel that includes: a first inlet; a first outlet; and a first chamber fluidly connected to the first inlet and the first outlet. The plurality of microchannels can comprise a second microchannel that includes: a second inlet; a second outlet; and a second chamber fluidly connected to the second inlet and the second outlet. The multichamber flow assembly can comprise a porous biocompatible membrane oriented along a longitudinal interface between the first microchannel and the second microchannel, wherein the porous biocompatible membrane is permeable for movement of biomolecules from the first chamber to the second chamber through the porous biocompatible membrane.

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal organoids were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

Means which enables preparation of a thick cell aggregate by a simple process without an operation of detaching and stacking of cells is disclosed. The method for preparing a three-dimensional cell aggregate by the present invention comprises: a cell encasing step of placing a cell suspension in a cell container; and a pressure application step of applying pressure to cells in the container. The cell encasing step and the pressure application step may be carried out a plurality of times. By the present invention, a thick, robust cell aggregate can be obtained by a simple operation of applying pressure to a cell suspension or a medium containing cells. Since the method does not require an operation of stacking a plurality of cell sheets, the cells are hardly damaged, and the conditions of the cells can be favorably maintained, so that the cells can be advantageously used as a tissue piece for transplantation.

Described are methods for producing multi-layered tubular tissue structures, tissue structures produced by the methods, and their use.