Abstract: The present invention relates to a cardiac cell culture model system composed of a cardiac organoid and blood or blood precursor cells. The cardiac cell culture model system serves as a model for the heart, and the present invention also relates to drug screening with the cardiac cell culture model system investigating the impact of the drug on the heart.

Abstract: The present invention relates to a preparation method for a self-organized cardiac organoid. The invention also relates to a cardiac tissue organoid obtained by the method and to its use in regenerative medicine, as a tissue implant, or in drug screening.

Abstract: The present invention relates to a non-agonist ligand, particularly an antibody, that specifically binds to MTHFD1L or an oligonucleotide suppressing expression of MTHFD1L for use in treatment of hypertrophic heart disease and failure. The invention also relates to a method for identifying a small-molecule inhibitor of MTHFD1L.

Abstract: The invention relates to a method for generating a cardiac tissue mimetic, comprising the steps of mixing cardiomyocytes (CM) and fibroblasts (FB) at a ratio from 2.5:1 to 10:1, thereby providing a first mixture, incubating said first mixture, such that said cardiomyocytes and said fibroblasts form a spherical structure, adding endothelial cells (EC) to said spherical structure at a ratio of cardiomyocytes (CM) to endothelial cells (EC) from 1.5:1 to 4:1, thereby providing a second mixture, and incubating said second mixture, such that a cardiac tissue mimetic is formed. The invention further relates to a cardiac tissue mimetic comprising cardiomyocytes (CM), endothelial cells (EC), and fibroblasts (FB), wherein said cardiac tissue mimetic comprises sarcomeric structures and vascular structures. Further aspects of the invention are the cardiac tissue mimetic for use in a method for heart tissue repair or replacement and a method for screening a compound using a cardiac tissue mimetic.

Abstract: A method for expression of transcribable unit(s) in a target cell is provided. The method comprises the steps of: a) providing a target cell expressing a site-specific recombinase, b) providing a DNA vector characterized by a 5? to 3? vector sequence orientation. The DNA vector comprises a plurality of recombination units, wherein a single recombination unit comprises at least one transcribable unit and a first type and a second type of target site that are recognizable by the site-specific recombinase. Recombination can only occur between two target sites of the same type and the first type of target site is located at the 5? start of the recombination unit and the second type of target site is located at the 3? end of the recombination unit. For all recombination units comprised within the DNA vector, the orientation of all of the first type of target sites are the same, and the orientation of all of the second type of target sites are the same.

Abstract: A method for expression of transcribable unit(s) in a target cell is provided. The method comprises the steps of: a) providing a target cell expressing a site-specific recombinase, b) providing a DNA vector characterized by a 5? to 3? vector sequence orientation. The DNA vector comprises a plurality of recombination units, wherein a single recombination unit comprises at least one transcribable unit and a first type and a second type of target site that are recognizable by the site-specific recombinase. Recombination can only occur between two target sites of the same type and the first type of target site is located at the 5? start of the recombination unit and the second type of target site is located at the 3? end of the recombination unit. For all recombination units comprised within the DNA vector, the orientation of all of the first type of target sites are the same, and the orientation of all of the second type of target sites are the same.