Abstract: The application describes methods for producing artificial skeletal muscle tissue from pluripotent stem cells. A method for producing skeletal myoblasts, skeletal myotubes and satellite cells from pluripotent stem cells is also disclosed. During the described methods, there is directed differentiation and maturation of the pluripotent stem cells into skeletal myotubes and satellite cells. The application also describes artificial skeletal muscle tissue which has multinuclear skeletal muscle fibres with satellite cells. Furthermore, the invention relates to mesodermally differentiated skeletal myoblast precursor cells, myogenically specified skeletal myoblast precursor cells, skeletal myoblast cells, satellite cells and skeletal myotubes, which can be produced by means of the disclosed methods. The application also describes the use of skeletal muscle tissue or the disclosed cells in drug testing or in medicine.

Abstract: A method for manufacturing a multilayer engineered heart muscle that includes (i) providing a liquid reconstitution mixture in a mould and (ii) culturing the mixture. The method includes a sequential addition of one or more further liquid reconstitution mixtures to obtain a multilayer engineered heart muscle. The muscle ideally has the form of a patch, a pouch, or a cylinder. Furthermore, a multilayer engineered heart muscle having collagen, cardiac myocytes and non-myocytes originating from at least 2 layers is disclosed. The multilayer engineered heart muscle forms the basis for several in vitro and in vivo applications such as the production of a multilayer engineered heart muscle for use in a patient, for example for use in heart repair.

Abstract: The present invention relates to the field of in vitro 3D modeling of neural tissues, particularly of the brain. There is the need of developing cell culture models of neural tissue that reflect physiological aspects of neural tissue. The present invention provides methods of producing bioengineered neuronal organoids (BENOs) which form functional neuronal networks. The present invention also relates to uses and applications of the produced BENOs, e.g., in the fields of drug screening and personalized medicine.

Abstract: The application describes a method for producing a population of cardiac stromal cells from pluripotent stem cells. Specifically, the method relates to (i) inducing epithelial-mesenchymal transition of pluripotent stem cell derived epicardial cells and (ii) amplifying the number of cardiac stromal cells in serum-free conditions. These cardiac stromal cells can be mass produced according to the described method and said cells maintain the expression of CD90, CD73 and CD44 in at least 80% of the cardiac stromal cells. Furthermore, the application relates to a population of cardiac stromal cells, which are pluripotent stem cells derived and wherein at least 80% of the cardiac stromal cells express CD90, CD73 and CD44. Said cardiac stromal form the basis for several in vitro and in vivo applications such as the production of engineered organ tissue and the support of, for example, heart repair. Also, a serum- free culture medium for the amplification of cardiac stromal cells is provided herein.

Abstract: A well plate comprises a plate main body and at least one cavity in an upper side of the plate main body. An upwardly open annular channel is formed in the at least one cavity, the annular channel being delimited at an inner circumference thereof by a closed circumferential wall. A horizontal outer circumference of the circumferential wall decreases from bottom to top up to an upper edge of the circumferential wall. Within the horizontal circumference of the circumferential wall, at its upper edge, at least two retaining elements connect upwardly to the upper edge of the circumferential wall. The at least two retaining elements are at a free horizontal distance to one another, and at least one of the at least two retaining elements is elastically supported at the plate main body in horizontal direction.

Abstract: The present invention provides a new method for producing Engineered Heart Muscle (EHM) under chemically fully defined conditions all compatible with GMP regulations. The resulting human myocardium generates force and shows typical heart muscle properties.

Abstract: The present disclosure concerns agents for use in a new therapeutic application for the prevention or treatment of cardiac arrhythmia and sudden cardiac death. More specifically, the present disclosure concerns an expression construct capable of enhancing expression of TBX5 in a subject to be treated, for use in the prevention or monotherapeutic treatment of a ventricular heart disease and associated complications selected from cardiac arrhythmia and sudden cardiac death.

Abstract: The invention is directed to a method for the preparation of a multiring engineered heart tissue construct suitable for use in cardiac tissue augmentation and/or replacement therapy. The invention further refers to multiring EHT constructs which comprise at least two force-generating engineered heart tissue rings fused with each other and a device for preparing the same. Finally, the invention relates to force-generating engineered heart tissue rings derived from human cells and their use in drug screening and target validation assays.

Abstract: The present invention provides a new method for producing Engineered Heart Muscle (EHM) under chemically fully defined conditions all compatible with GMP regulations. The resulting human myocardium generates force and shows typical heart muscle properties.

Abstract: The present invention relates to the field of in vitro 3D modeling of neural tissues, particularly of the brain. There is the need of developing cell culture models of neural tissue that reflect physiological aspects of neural tissue. The present invention provides methods of producing bioengineered neuronal organoids (BENOs) which form functional neuronal networks. The present invention also relates to uses and applications of the produced BENOs, e.g., in the fields of drug screening and personalized medicine.

Abstract: The invention is directed to a pouch-like construct comprising mammalian tissue which can be used for preventing distension and/or resisting dilation of the heart in a mammal. Preferably, the pouch-like tissue construct has contractile properties. The invention further relates to a method for the preparation of a pouch-like construct comprising mammalian tissue which can be used for the above purposes.

Abstract: The invention is directed to a method for the preparation of a multiring engineered heart tissue construct suitable for use in cardiac tissue augmentation and/or replacement therapy. The invention further refers to multiring EHT constructs which comprise at least two force-generating engineered heart tissue rings fused with each other and a device for preparing the same. Finally, the invention relates to force-generating engineered heart tissue rings derived from human cells and their use in drug screening and target validation assays.

Abstract: The present invention provides a new method for producing Engineered Heart Muscle (EHM) under chemically fully defined conditions and compounds all compatible with GMP regulations. The resulting human myocardium generates force and shows typical heart muscle properties.

Abstract: The present invention relates to a pouch-like structure useful for mechanically preventing distension and/or resisting dilation of the heart and for supporting the hearts function by controllable and paracrine support of a failing heart in a mammal. The pouch-like structure is composed at least partly of engineered tissue comprising genetically engineered cells, such as genetically engineered cells other than cardiac myocytes whereby said genetically engineered cells contain a gene encoding a paracrine factor, said gene encoding the paracrine factor being under control of an inducible promoter system or a heterologous promoter system. Further, the present invention relates to a method for the preparation of the pouch-like structure for therapeutic, disease modelling, and drug development applications. In addition, the present invention relates to cells other than cardiac myocytes for use in the preparation of the pouch-like structure as described herein.

Abstract: The invention is directed to a pouch-like construct comprising mammalian tissue which can be used for preventing distension and/or resisting dilation of the heart in a mammal. Preferably, the pouch-like tissue construct has contractile properties. The invention further relates to a method for the preparation of a pouch-like construct comprising mammalian tissue which can be used for the above purposes.

Abstract: The invention is directed to a method for the preparation of a multiring engineered heart tissue construct suitable for use in cardiac tissue augmentation and/or replacement therapy. The invention further refers to multiring EHT constructs which comprise at least two force-generating engineered heart tissue rings fused with each other and a device for preparing the same. Finally, the invention relates to force-generating engineered heart tissue rings derived human cells and their use in drug screening and target validation assays.

Abstract: The present invention is directed to a method for producing bioengineered heart muscle (BHM) from pluripotent stem cells, generally comprising the steps of inducing mesoderm differentiation, cardiac differentiation, and cardiac maturation by directed tissue formation. The method is a robust, serum-free and reproducible way to produce BHM for multiple applications, and is applicable to multiple pluripotent stem cell lines. The present invention is also directed to the BHM produced by the method disclosed herein, as well as to uses of said BHM in pharmacologic and toxicity screenings, and its use in medicine.

Abstract: The present invention is directed to a method for producing bioengineered heart muscle (BHM) from pluripotent stem cells, generally comprising the steps of inducing mesoderm differentiation, cardiac differentiation, and cardiac maturation by directed tissue formation. The method is a robust, serum-free and reproducible way to produce BHM for multiple applications, and is applicable to multiple pluripotent stem cell lines. The present invention is also directed to the BHM produced by the method disclosed herein, as well as to uses of said BHM in pharmacologic and toxicity screenings, and its use in medicine.

Abstract: A well plate comprises a plate main body and at least one cavity in an upper side of the plate main body. An upwardly open annular channel is formed in the at least one cavity, the annular channel being delimited at an inner circumference thereof by a closed circumferential wall. A horizontal outer circumference of the circumferential wall decreases from bottom to top up to an upper edge of the circumferential wall. Within the horizontal circumference of the circumferential wall, at its upper edge, at least two retaining elements connect upwardly to the upper edge of the circumferential wall. The at least two retaining elements are at a free horizontal distance to one another, and at least one of the at least two retaining elements is elastically supported at the plate main body in horizontal direction.

Abstract: The invention is directed to a method for the preparation of a multiring engineered heart tissue construct suitable for use in cardiac tissue augmentation and/or replacement therapy. The invention further refers to multiring EHT constructs which comprise at least two force-generating engineered heart tissue rings fused with each other and a device for preparing the same. Finally, the invention relates to force-generating engineered heart tissue rings derived from human cells and their use in drug screening and target validation assays.