This disclosure relates generally to the differentiation of human pluripotent stem cells, and more particularly to a method of spatially adsorbing morphogens to differentiate human pluripotent stem cells.

Described herein are compositions and methods related to use of cardiosphere-derived cells and their extracellular vesicles, such as exosomes and microvesicles, for achieving anti-aging and rejuvenation. This includes discoveries for effects on heart structure, function, gene expression, and systemic parameters. For animal studies, intra-cardiac injections of neonatal rat CDCs was compared to in old and young rats including evaluation of blood, echocardiographic, haemodynamic and treadmill stress tests. For in vitro studies, human heart progenitors from older donors, or cardiomyocytes from aged rats were exposed to human CDCs or cardiosphere derived cell (CDC) derived exosomes (CDC-XO) from pediatric donors. CDCs and CDC-XOs were capable of effectuating youthful patterns of gene expression in the hearts of old, along with a variant of physiological and function benefits, including elongation of telomere length. Together, these results indicate capacity of CDCs and CDC-XO to ward off the effects of aging through rejuvenation.

The disclosure generally relates to methods for generating cardiac fibroblast cells from epicardial cardiac progenitor cells, populations of cardiac fibroblast cells and uses thereof.

A method for promoting conversion of cells into cardiomyocytic tissue is carried out by contacting fibrotic tissue (e.g., scar tissue) with a microRNA oligonucleotide or combination of microRNA oligonucleotides. The methods lead to direct reprogramming of fibroblasts to cardiomyocytes or cardiomyoblasts.

A composition includes porous silica particles to carry a cell fate modulating factor therein. A method for modulating cell fate includes treating various cells with the composition. The cell fate modulating factor is delivered to a stable target receptor, toxicity to subject cells for delivery may be reduced, a fate of the subject cells can be controlled through sustained release of at least 99 wt. % of the cell fate modulating factor.

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.

Embodiments of the disclosure concern compositions and methods of use related to particular immortalized cells, including cardiac stem cells, obtained from a pediatric or neonatal individual. In specific embodiments, the immortalized cells, or conditioned medium from the cells, or partial or total secretomes thereof, are provided in an effective amount to an individual in need thereof either alone or in combination with cardiac stem cells.

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.

Disclosed herein are compositions and methods for cellular reprogramming. The compositions comprise one or more miRs and an activator of NFκB. Also provided are methods for enhancing or upregulating cardiomyocyte maturation in a cell or a subject and methods for inhibiting or downregulating cardiomyocyte maturation.

An aspect of the present invention makes it possible to easily observe both surfaces of a cell sheet in a condition in which the cell sheet is at a stable position in a culture medium. A cell sheet production device (100) includes: a container (20); and a support unit (10) removably held in the container (20), the support unit (10) including a mesh sheet (2) and a base (3) which holds the mesh sheet (2) such that the mesh sheet (2) floats from a bottom surface of the container (20), the support unit (10) being held in the container (20) such that the support unit is at a fixed position in vertical and horizontal directions in a culture medium.