The disclosure generally relates to methods, cells, and compositions for preparing cardiac extracellular matrix. In particular, provided herein are methods for preparing a cardiac extracellular matrix using SUSD2 High fibroblasts and SUSD2 High myofibroblasts.

The present disclosure relates to a scaffold for culturing and transplanting a cardiac organoid by using a heart extracellular matrix (HEM).

Several embodiments relate to methods of repairing and/or regenerating damaged or diseased tissue comprising administering to the damaged or diseased tissues compositions comprising exosomes. In several embodiments, the exosomes comprise one or more microRNA that result in alterations in gene or protein expression, which in turn result in improved cell or tissue viability and/or function.

Described herein are compositions and techniques related to generation and therapeutic application of stem cell-derived exosomes. The Inventors have discovered cardiosphere-derived cells (CDCs) and their secreted exosomes mediate such inflammatory processes, by, for example, shifting macrophages away from a proinflammatory M1 phenotype toward M2 healing phenotype. This suggests compositions and techniques for use in both long-term reversal of heart and vascular disease pathology, and protection against such disease progression via modulation of inflammation and immune responses.

The present invention provides: a method for producing mixed cells comprising cardiomyocytes, endothelial cells and mural cells from induced pluripotent stem cells, the method comprising (a) a step of producing cardiomyocytes from induced pluripotent stem cells and (b) a step of culturing the cardiomyocytes in the presence of VEGF; and a therapeutic agent for heart diseases, comprising the mixed cells produced by the method.

The present disclosure provides ex vivo chamber-specific cardiac tissues, methods for generating the cardiac tissues in a bioreactor, and methods of using the cardiac tissues. Examples of cardiac tissues that can be generated include, but are not limited to, atrial tissues, ventricular tissues, and composite tissues having an atrial tissue connected to a ventricular tissue.

This invention relates to three-dimensional myocardial infarct organoids and methods of making and using the same for screening compounds that improve cardiac function and compounds that diminish cardiac function.

A bioreactor and methods for use can include a microfibrous scaffold, that can be made of a composite bioink, and that can have endothelial cells directly embedded within the scaffold using an additive manufacturing process. The scaffold can further be seeded with cardiomyocytes. The hydrogel scaffold can be composed of a plurality of serpentine layers, with each serpentine layers, which can be placed on each other in a cross-hatch configuration, so that the primary axes of successive layers are perpendicular. This configuration can establish an aspect ratio for the scaffold, which can be selectively varied. For greater strength, the successive layers that have a primary axis in the same direction can be placed in the scaffold so that they are slight offset from each other. The scaffold can be placed in the bioreactor with perfusion, for use in cardiovascular drug screening and other nanomedicine endeavors.

Several embodiments relate to methods of repairing and/or regenerating damaged or diseased tissue comprising administering to the damaged or diseased tissues compositions comprising exosomes. In several embodiments, the exosomes comprise one or more microRNA that result in alterations in gene or protein expression, which in tum result in improved cell or tissue viability and/or function.

The present invention relates to a method for producing endothelial cells, including carrying out: (a) inducing a population of mesoderm-lineage cells containing endothelial progenitor cells from pluripotent stem cells without forming an embryoid body; and (b) culturing the population of mesoderm-lineage cells containing endothelial progenitor cells in the presence of RepSox, in this order. According to the present invention, endothelial cells with high quality can be efficiently produced from pluripotent stem cells. The endothelial cells obtained by the method of the present invention are useful for the production of, for example, a myocardial sheet, and expected to be utilized in the treatment of a heart disease. A myocardial sheet can be produced by mixing the endothelial cells obtained by the method of the present invention with myocardial cells and mural cells and culturing the cells.