The present invention provides a basal cell culture medium and a feed medium with novel amino acid ratios and/or iron choline citrate as iron carrier that result in improved performance of mammalian cell culture processes, such as CHO cultivation and protein production processes, in particular in increased product titer (e.g. of monoclonal antibodies). Also provided are methods for culturing mammalian cells and producing a protein of interest using said basal cell culture medium and optionally feed medium. The invention also provides for a medium platform that comprises (i) the basal cell culture medium and (ii) the feed medium.

Described herein are specific CHO genomic sites for targeted insertion of exogenous genes. The sites are located within a sequence selected from SEQ ID NOs: 1-16.

The present disclosure features methods and compositions for modulating lipid metabolism to achieve improved production and quality of recombinant products, such as next generation biologics. Modulation of lipid metabolism as described herein includes, for example, introducing a lipid metabolism modulator described herein to a cell or a cell-free system. Also encompassed by the present disclosure are engineered cells with improved production capacity and improved product quality, methods for engineering such cells, and preparations and mixtures comprising the products from such cells.

Described are engineered cells that include genetic alterations leading to up- or down-regulation of certain genes in the cells for improved production of a recombinant protein, especially one that is not easily expressed at high levels in unaltered cell lines. Also provided are methods of preparing and using such cells.

Disclosed herein are methods for obtaining endometrial stromal fibroblast cells from pluripotent stem cells, such as induced pluripotent stem cells. The present disclosure also provides methods of obtaining a three-dimensional, multilayered endometrial tissue composition. Methods of using the cells and tissue compositions in drug screening and therapeutic applications are also provided.

The invention relates to a serum-free cell culture perfusion medium comprising the medium components subgrouped into at least three separate aqueous concentrated feeds and a diluent, wherein the resulting serum-free cell culture perfusion medium is pH-adjusting to neutral pH upon mixing. Also provided is a method of preparing said serum-free cell culture perfusion medium. The invention further relates to methods of culturing mammalian cells or producing a protein of interest in perfusion culture using said serum-free cell culture perfusion medium that achieve high productivity at a low cell specific perfusion rate. The invention further relates to the use of the new and improved serum-free cell culture perfusion medium to control osmolality in a perfusion cell culture, wherein increasing osmolality results in an increase in total productivity and/or cell specific productivity by suppressing cell growth during cell culture, e.g., during production phase of perfusion cell culture. Suppression of cell growth particularly reduces or eliminates the need for wasteful cell bleed.

The current invention reports the use of meta-tyrosine for increasing the specific productivity of a eukaryotic cell that produces/expresses a polypeptide. In the current method it is not necessary to perform a temperature-, osmolality- or pH shift or to add drugs like valproic acid or sodium butyrate to modulate the specific productivity of the cultivated cells. The method does not affect cell viability or product titer.

The present disclosure relates generally to therapeutic agents that may be useful as modulators of Integrated Stress Response (ISR) pathway.

The present invention relates to the identification of a genomic integration site for heterologous polynucleotides in Chinese Hamster Ovary (CHO) cells resulting in high RNA and/or protein production. More specifically it relates to CHO cells comprising at least one heterologous polynucleotide stably integrated into the S100A gene cluster of the CHO genome and to methods for the production of said CHO cells. Further, the invention relates to a method for the production of a protein of interest using said CHO cell and to the use of said CHO cell for producing a protein of interest at high yield. Integration within these specific target regions leads to reliable, stable and high yielding production of an RNA and/or protein of interest, encoded by the heterologous polynucleotide.

The present disclosure provides a method for promoting the growth of parietal decidual basalis-mesenchymal stem cells (PDB-MSCs), which comprises promoting the growth of parietal decidual basalis-mesenchymal stem cells (PDB-MSCs) via a human umbilical cord-mesenchymal stem cell (UC-MSC)-derived exosome. In the present disclosure, after the PDB-MSCs are co-cultivated with the human UC-MSC-derived exosome, the PDB-MSCs show strong cell proliferation ability, prominent cell shape, and desirable cell viability. That is, the human UC-MSC-derived exosome of the present disclosure can improve a quality of PDB-MSCs and effectively improve the ability of PDB-MSCs to secrete vascular endothelial growth factor (VEGF) and stem cell factor (SCF), so as to solve the problem that PDB-MSCs show decreased proliferation ability and poor cell viability after multiple passages, which effectively facilitates the large-scale cultivation and clinical practice of PDB-MSCs.