An organ implant, such as a heart implant, including a support structure having a plurality of pores and defining passages configured for the growth of blood vessels; and stem cells from at least one soft tissue source of a patient deposited into the pores of the support structure is described. The implant is configured to repair a portion of an organ of the patient.

Provided herein is a method for making a tissue engineering scaffold. The method includes layering at least one sheet of cells onto a flexible scaffold, casting the sheets into geometries, and thereby creating the tissue engineering scaffold. Preferred geometry are non-linear (i.e. not a substantially flat surface such as may be provided by a flat glass substrate). The flexible scaffold is characterized by tensile strength, viscosity, stress, strain, modulus of polymers, or any combination thereof.

A method of forming a tissue. The method includes providing a source of a pre-tissue composition comprising endothelial cells. The method also includes perfusing a culture media into the pre-tissue composition using a plurality of primary channels and a plurality of secondary channels to form the tissue, wherein the endothelial cells are configured to form the secondary channels via vasculogenesis.

Provided is a cell structure including: a connective tissue structure; and an epithelial structure placed on the connective tissue structure, in which the connective tissue structure contains a fragmented extracellular matrix component and first cells including mesenchymal cells, at least a part of the fragmented extracellular matrix component is placed between the first cells, and the epithelial structure contains epithelial cells.

The present invention provides a method of constituting a tissue construct in vitro using a tissue without depending on scaffold materials. A method of integrating a biological tissue with a vascular system in vitro, comprising coculturing a biological tissue with vascular cells and mesenchymal cells. A biological tissue which has been integrated with a vascular system by the above-described method. A method of preparing a tissue or an organ, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of regeneration or function recovery of a tissue or an organ, comprising transplanting the biological tissue described above into a human or a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of preparing a non-human chimeric animal, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or organ in which vascular networks have been constructed. A method of evaluating a drug, comprising using at least one member selected from the group consisting of the biological tissue described above, the tissue or organ prepared by the method described above, and the non-human chimeric animal prepared by the method described above. A composition for regenerative medicine, comprising a biological tissue which has been integrated with a vascular system by the method described above.

Provided is a method for producing a three-dimensional tissue having a vascular system structure, said method comprising: (a) a step for forming a vascular system structure template using a gel; (b) a step for forming a three-dimensional tissue in the vicinity of the template; (c) a step for dissolving the template using a cationic solution; and (d) a step for seeding vascular endothelial cells and/or lymphatic vessel endothelial cells in a void remaining after the dissolution of the template. Also provided is a method for producing a three-dimensional tissue having a vascular system structure, said method comprising: (i) a step for forming a vascular system structure template using a gel; (ii) a step for seeding vascular endothelial cells and/or lymphatic vessel endothelial cells on the template; (iii) a step for forming a three-dimensional tissue in the vicinity of the cells seeded above; and (iv) a step for dissolving the template using a cationic solution. Also provided is a three-dimensional tissue comprising a gel which has a vascular system structure.

A method of vascularising a cell aggregate on a microfluidic device, microfluidic cell culture devices comprising perfusable vascular networks and kits and assays using the microfluidic cell culture devices are described. The microfluidic devices comprise one or more capillary pressure barriers allowing for formation of an extracellular matrix gel within a confined area of the network, in which cells can be cultured for different uses.

Provided herein are novel organoid culture media, organoid culture systems, and methods of culturing tumor organoids using the subject organoid culture media. Also provided herein are tumor organoids developed using such organoid culture systems, methods for assessing the clonal diversity of the tumor organoids, and methods for using such tumor organoids, for example, for tumor modelling and drug development applications. In particular embodiments, the tumor organoid culture media provided herein is substantially free of R-spondins (e.g., R-spondin1).

Methods are provided for the efficient differentiation of hPSCs into HSC-like cells and endothelial cells in defined, monolayer conditions solely using extracellular signals to guide differentiation. The instant disclosure also provides methods of screening for cellular responses of the generated hematopoietic stem cells, endothelial cells and derivatives thereof. Treatment methods making use of the generated hematopoietic stem cells and endothelial cells are also provided. The instant disclosure also provides systems, compositions, and kits for practicing the methods of the disclosure.

Microfluidic devices with open ports and gel channels for forming perfusable hydrogel vascular networks with holes or ports for samples, and methods of making and using, are provided which integrate interstitial flows to an ex vivo vascularized tissue model. Samples of cells, spheroids, organoids, and tissues can be used for screening of agents for efficacy, toxicity and dosage. The devices create interstitial flow from the top of the gel hole, through the sample toward the vascular networks, and/or luminal flows generated by a pressure difference between two media channels across the vascular network. This system is useful for studying angiogenesis, immune cell migration and testing new immunotherapy drug candidates.