The present disclosure relates to the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS) and diseases related to vascular ageing and in the treatment of smooth muscle cells diseases, in particular an inhibitor of a metalloprotease the treatment of smooth muscle cells diseases. The disclosure subject matter describes a more effective therapies for the treatment of Hutchinson-Gilford Progeria Syndrome and diseases related to vascular ageing, or namely by the use of an inhibitor of a metalloprotease.

The present disclosure relates generally to recombinant cardiomyocytes and cardiomyocyte cell lines overexpressing hERG and uses thereof.

Disclosed are subpopulations of mammalian stem cell- or mammalian progenitor cell-derived cardiomyocytes. The subpopulations of cardiomyocytes contain a portion of a population of mammalian stem cell- or mammalian progenitor cell-derived cardiomyocytes. The subpopulations of cardiomyocytes can be CD36.sup.+ subpopulations or CD36.sup.− subpopulations. Disclosed are methods of isolating and of using the subpopulations of cardiomyocytes, particularly in cardiac disease modeling, drug screening, cardiotoxicity testing, and cardiac regeneration/repair.

A method to increase the efficiency of myotube generation and maturation from pluripotent stem cells comprising: (a) differentiating pluripotent stem cells to myogenic progenitors; and (b) terminally differentiating said myogenic progenitors from (a) into myotubes in the presence of at least one gamma secretase inhibitor, wherein myotube generation is increased in the presence of at least one gamma secretase inhibitor, as compared to differentiation in the absence of gamma secretase inhibitors.

The present disclosure provides compositions and methods based on the use of 15-PGDH as a therapeutic target in rejuvenation of aging non-skeletal muscle tissues and/or organs. The 15-PGDH inhibitor SW033291 administered intraperitoneally for 4 weeks resulted in restoration of follicular structure and re-establishment of the marginal zone in spleens of 25 month old mice. Treatment of 25 month old mice with SW033291 also reduced the levels of IL10, IL6, BTC, GM-CSF, IL 13 back to levels similar 0 to 4 month old mice.

The present invention provides methods for assessing a compound's potential toxicity.

Disclosed herein are agents that enhance muscle stem cell engraftment, as well as methods and compositions using the same.

A developmental toxicity screening assay using spatially organized cardiac organoids with contracting cardiomyocytes in the center surrounded by stromal cells distributed along the pattern perimeter engineered from human induced pluripotent stem cells (hiPSCs). Cardiac organoids generated from 600 μm-diameter circles were used as a developmental toxicity screening assay for the quantification of the embryotoxic potential of nine pharmaceutical compounds. The cardiac organoids were demonstrated as having a potential use as an in vitro platform for studying organoid structure-function relationships, developmental processes, and drug-induced cardiac developmental toxicity.

The present invention relates to a multicellular construct that includes cells and a scaffold. The scaffold is constituted by a layered composite that comprises a gelatin nonwoven containing gelatin as a main component, and a gelatin film containing gelatin as a main component and layered on one surface of the gelatin nonwoven, and the cells are present in at least one of a region on the surface of the gelatin nonwoven and a region inside the nonwoven. The multicellular construct can be produced by arranging the scaffold in a swollen state inside the culture vessel whose inner surface is in the dry state such that the gelatin film of the scaffold is in contact with the inner bottom surface of the culture vessel, dripping a cell suspension onto the gelatin nonwoven of the scaffold, and then culturing the cells. This makes it possible to provide a multicellular construct with high seeding efficiency in which desorption of cells from a scaffold is suppressed, a method for manufacturing the same, a kit for producing the same, and a method for evaluating a compound using the same.

Provided herein are recombinant cardiomyocytes and cardiomyocyte cell lines expressing human Ether-a-go-go Related Gene (hERG) potassium ion channel, including, for example, stable cell lines, that comprise a transfected or transduced nucleic acid sequence encoding hERG. Also provided herein are methods of using the recombinant cardiomyocytes and cardiomyocyte cell lines expressing hERG for screening compounds for cardiotoxicity, including methods for determining the activity of compounds to inhibit hERG.