A cell culture apparatus is provided, including a storage tank including one or a plurality of cell culture units, in which the cell culture unit includes a culture chamber having an inner surface-side space in which a culture solution is stored, a permeable membrane having a first surface to which cells are adherable and a second surface opposite to the first surface, the first surface facing the inner surface-side space, a culture solution storage chamber that stores the culture solution, a culture solution introduction flow path that introduces the culture solution in the culture solution storage chamber to the inner surface-side space, and a culture solution discharge flow path that sends, to the culture solution storage chamber, the culture solution which permeates through the membrane from the inner surface-side space and flows into an outer surface-side space that the second surface of the membrane faces.

Disclosed herein are methods for introducing functional mitochondria into liver cells in living animals (e.g., mammals). The disclosed compositions and methods can be used to treat clinical conditions characterized by genetic or acquired mitochondrial defects and the resulting dysfunctions and diseases therefrom.

The invention is directed to methods for culturing cells so that the cells are induced to differentiate into cells that express a hepatic stellate phenotype. The invention is also directed to cells produced by the methods of the invention. The cells are useful, among other applications, for treatment of liver deficiencies, liver metabolism studies, and liver toxicity studies, fibrogenic studies, or to support hepatocyte function in co-culture setting.

The present invention provides a product comprising plated human hepatocytes on a surface and at least some of the plated hepatocytes are in one or more hepatocyte clusters on feeder cells, which are attached to the surface. A method of preparing plated human hepatocytes is also provided. The preparation method comprises applying human hepatocytes to a surface in the presence of feeder cells, co-culturing the applied hepatocytes with the feeder cells, and forming one or more hepatocyte clusters by the co-cultured hepatocytes on the feeder cells, which are attached to the surface. The plated hepatocytes may be used for various purposes, including the preparation of a hepatitis B virus (HBV) infected hepatocyte culture model and drug testing.

The present invention features compositions and methods for editing deleterious mutations associated with alpha-1 anti-trypsin (A1AT) deficiency. In particular embodiments, the invention provides methods for correcting mutations in an A1AT polynucleotide using an adenosine deaminase base editor, ABE8, having unprecedented levels of efficiency.

A method for inducing reprogramming of a cell of a first type which is not a non-hepatocyte (non-hepatocyte cell), into a cell with functional hepatic drug metabolizing and transporting capabilities, is disclosed. The non-hepatocyte is induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte cell culture medium and hepatocyte maturation medium for a sufficient period of time to convert the non-hepatocyte cell into a cell with hepatocyte-like properties. The iHeps induced according to the methods disclosed herein are functional induced hepatocytes (iHeps) in that they express I and II drug-metabolizing enzymes and phase III drug transporters and show superior drug metabolizing activity compared to iHeps obtained by prior art methods. The iHeps thus provide a cell resource for pharmaceutical applications.

In order to induce aging while cutting the costs associated with adding cytokines at different aging stages, in a system for aging induction including a first culture chamber for perfusing, with a culture medium, a subject of aging-induction, the subject of aging-induction being derived from a living organism; a second culture chamber for perfusing, with a culture medium, a secretor that secretes a cytokine; and a control device for aging induction including a detection unit, a memory unit and a control unit, a protocol for aging induction defining a procedure of aging induction is stored, and in the control unit, an aging state of the subject of aging-induction is detected with a detection unit, and based on the protocol for aging induction, a flow rate at which the culture medium containing the cytokine secreted by the secretor is supplied to the subject of aging-induction is controlled according to the aging state of the subject of aging-induction.

The present invention provides methods of inducing proliferation of and/or differentiating cells comprising contacting cells with compounds within the methods of the invention. The present invention further provides cells obtainable by the methods of the invention.

Provided herein relates to devices for simulating a function of a tissue and methods of using the same. In some embodiments, the devices can be used to simulate a function of a human liver tissue. In some embodiments, the devices can be used to simulate a function of a dog liver tissue. Endothelial cell culture media for long-term culture of endothelial cells are also described herein.

Provided herein are compositions and methods of using base editors comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain in conjunction with a guide polynucleotide. Also provided herein are base editor systems for editing nucleobases of target nucleotide sequences.