An object of the present invention is to provide an endodermal cell population for obtaining optimal somatic cells as cell therapy preparations. The endodermal cell population of the present invention has a reduced content proportion of undifferentiated cells in the cell population and contains endodermal cells differentiable into optimal somatic cells as cell therapy preparations. Further, a somatic cell derived from the endodermal cell population of the present invention has excellent therapeutic effects as a cell therapy preparation.

The invention relates to a method of cultivating spirulina (Arthrospira platensis) in a temperate or northern climate, comprising a period of reproduction of the spirulina strain and a period of dormancy of the spirulina strain when the night temperature of the cultivation tank falls below the limit of 17° C., preferably below the limit of 18° C. or 19° C. or even 20° C., in which, in order to put said spirulina strain into dormancy, a sample volume of the reproduction medium of said strain is taken and placed in conditions of reduced luminosity compared to a sunlight of normal intensity generally borne by said strain during the reproduction period during periods of light alternating with periods of darkness, the said sampling volume is maintained at a temperature of between 5 and 20° C., preferably between 10 and 18° C., under reduced agitation compared with agitation during the reproduction period, at a pH of at least 9, preferably at least 9.5 or at least 10 feeding the sample volume every 4 to 7 days with 5-15%, preferably 10%, of the sample volume of a composition comprising about 1 g/L sea salt, 6 g/L sodium bicarbonate, 2.5 g/L potassium nitrate, 1 g/L potassium sulfate and/or magnesium sulfate, and about 3 g/L sodium and/or calcium carbonate.

Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH.sub.4.sup.+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

The invention relates to a method of culturing mammalian cells expressing a heterologous protein in a perfusion cell culture comprising adding iron and a retinoid to reduce wasteful cell bleed during production phase. The invention further relates to a serum-free perfusion medium comprising iron and a retinoid and its use for culturing cells in a perfusion culture during production phase or for reducing the cell bleed volume during production phase.

Provided is a new use of a TGF-β small molecule inhibitor in the field of neuroregeneration, which can be used for the in vitro regeneration and directed differentiation of various nerve cells and brain-like organs. By adding same to a set of basal media having clear chemical compositions. pluripotent stem cells can be induced into adult cells derived from a variety of neural stem cells, and the number of induced nerve cells and the size of organoids can be greatly increased. The induction system provided in the present invention expands new functions of a single small molecule in the field of ectodermal cell induction and differentiation and at the same time avoids the use of B27 and other serum substitutes, thereby completely avoiding the potential risks caused by the presence of animal-derived components in cell culture processes, and greatly expanding the clinical prospects of a variety of nerve cell transplantations.

Phosphate-regulated expression of recombinant glycoprotein antigens and other recombinant proteins in diatoms is described herein. More specifically, described herein is the expression and purification of glycosylated, immunogenic, and serologically active receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, as well as SARS-CoV-2 nucleocapsid protein, in the marine pennate diatom Phaeodactylum tricornutum, as well as a functional lateral flow assay-based diagnostic device based on the produced recombinant RBD and nucleocapsid protein. Also described herein is the use of phosphate/iron levels in culture media to regulate expression/secretion of recombinant proteins under control of an HASP1 promoter in P. tricornutum or other suitable host cells. Also described herein is a method for increasing the expression/secretion of a recombinant protein by engineering the recombinant protein to lack a Tobacco Etch Virus (TEV) protease cleavage site.

Disclosures herein are directed to chemically defined animal-derived component free supplements designed for individual cell types that supports the ex vivo growth of cells as well or better than serum, in chemically defined conditions.

An expression system and process for the production of Diphtheria toxin polypeptides or mutated forms thereof, such as the toxoid CRM197 polypeptide, in genetically-modified E. coli with high yield is described. The system and process is based on the uncoupling of biomass growth from recombinant protein induction, i.e. using an inducer of protein production that cannot be used as a carbon source for growth by the bacteria. The use of specific components and conditions that improve protein yields are also described.

A large amount of cardiomyocyte spheroids is obtained from dissociated cardiomyocytes in a simple manner, in a short time, without using a special culture medium component, and without using a complicatedly-shaped container or a minute container. The problems can be solved by a method for producing cardiomyocyte spheroids, the method including allowing dissociated cardiomyocytes to flow under suspension conditions in a non-annular container to aggregate the cells. In addition, the problems can also be solved by a method for producing cardiomyocyte spheroids, in which the dissociated cardiomyocytes have a history of stabilization culture after thawing.

An object of the present invention is to provide an endodermal cell population for obtaining optimal somatic cells as cell therapy preparations. The endodermal cell population of the present invention has a reduced content proportion of undifferentiated cells in the cell population and contains endodermal cells differentiable into optimal somatic cells as cell therapy preparations. Further, a somatic cell derived from the endodermal cell population of the present invention has excellent therapeutic effects as a cell therapy preparation.