The present disclosure provides the sequence of a Paenibacillus polymyxa preproenzyme which is the precursor of a neutral protease, expression thereof in a transformed host organism, and methods for production of the neutral protease, by recombinant means. Further, use of the recombinantly produced neutral protease is disclosed in the field of cell biology, particularly for the purpose of tissue dissociation. The disclosure also includes blends with other proteases. Further disclosed are nucleotide sequences encoding the neutral protease.

The present invention relates generally to a three-dimensional cell and tissue culture system for the female reproductive tract. In particular provided herein the system includes individual female reproductive cultures in a dynamic microfluidic setting or integrated using a microfluidic microphysiologic system. In some embodiments, the present invention provides ex-vivo female reproductive tract integration in a three dimensional (3D) microphysiologic system.

Disclosed are compositions, in particular, organoid compositions, derived from more than one donor cell. Further disclosed are methods of making compositions, for example, organoid compositions, that comprise a differentiated cell population derived from more than one donor cell. Donor cells may include, for example, a precursor cell such as an embryonic stem cell or other precursor cell. The disclosed methods use synchronization conditions to produce a synchronized pooled-precursor cell population, which may then be differentiated into an organoid composition. Methods of using the compositions are also disclosed.

The present invention relates to microfluidic fluidic systems and methods for the in vitro modeling diseases of the lung and small airway. In one embodiment, the invention relates to a system for testing responses of a microfluidic Small Airway-on-Chip infected with one or more infectious agents (e.g. respiratory viruses) as a model of respiratory disease exacerbation (e.g. asthma exacerbation). In one embodiment, this disease model on a microfluidic chip allows for a) the testing of anti-inflammatory and/or anti-viral compounds introduced into the system, as well as b) the monitoring of the participation, recruitment and/or movement of immune cells, including the transmigration of cells. In particular, this system provides, in one embodiment, an in-vitro platform for modeling severe asthma as “Severe Asthma-on-Chip.” In some embodiments, this invention provides a model of viral-induced asthma in humans for use in identifying potentially effective treatments.

An object of the present invention is to provide an animal cell with improved proliferation ability and survival rate, a method for producing the animal cell, and a method for producing a target protein formed of the animal cell. According to the present invention, there is provided an animal cell having a gene encoding a target protein and a foreign gene encoding an isovaleryl-CoA dehydrogenase, in which the isovaleryl-CoA dehydrogenase is overexpressed.

This disclosure provides a cell culture media extending material capable of releasing nutrients into the cell culture environment slowly overtime. In embodiments, this material is a part of a cell culture vessel. In embodiments, the material is a coating or a film on a surface of a cell culture material. In additional embodiments, the material is a surface upon which cells are cultured, such as a cell culture vessel or a microcarrier.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a Serine Protease Inhibitor Kazal-type (SPINK) polypeptide (e.g., a SPINK5 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of Netherton Syndrome); and articles of manufacture or kits thereof.

The present invention relates to a novel bioreactor system for preparing an engineered three- dimensional biological tissue construct. The bioreactor system comprises a cultivation chamber that is designed to allow the formation, cultivation and the subsequent testing and/or stimulation of tissue constructs on one or more support elements with a minimum risk of microbial contamination or mechanical damage The invention furthermore relates to a method for preparing an engineered tissue construct using the novel bioreactor system. The invention also relates to the use of the bioreactor system for preparing engineered biological tissue constructs, preferably tissue constructs which are suitable for being used in clinical tissue replacement and reconstructive therapy, drug development, drug screening, toxicity testing, cosmetic studies, safety testing, developmental studies, disease modeling, or food purposes.

The invention provides a method for constructing a hepatic progenitor cell-like cell bank, including successively performing following processes to human primary hepatocyte cultures from different donor sources: transformation-culture, cryopreservation treatment, proliferation-culture, a first subculture treatment, virus infection, a second subculture treatment, continuous selection-culture and continuous subculture. In the method for constructing a heterogenous immortal hepatic progenitor cell-like cell bank of the present invention, the human primary hepatocyte culture of each of the donor sources is transformation-cultured before the proliferation-culture, which is beneficial in endowing the human primary hepatocyte cultures with good proliferation performance. Once combined with subsequent controlling of culture parameter, the immortal hepatic progenitor cell-like cell lines obtained from different donor sources may have good in vitro proliferation ability. The invention also provides an application of the hepatic progenitor cell-like cell bank and cell lines obtained by the construction method.

Disclosed herein are methods for directing a differentiation protocol to produce cells of a desired cell fate, such as SC-β and/or SC-α cells.