Despite their practical and commercial relevance, there are few reports on the kinetics of growth and production of Chinese hamster ovary (CHO) cells—the most frequently used host for the industrial production of therapeutic proteins. We characterize the kinetics of cell growth, substrate consumption, and product formation in naive and monoclonal antibody (mAb) producing recombinant CHO cells. Culture experiments were performed in 125 mL shake flasks on commercial culture medium (CD Opti CHO™ Invitrogen, Carlsbad, CA, USA) diluted to different glucose concentrations (1.2–4.8 g/L). The time evolution of cell, glucose, lactic acid concentration and monoclonal antibody concentrations was monitored on a daily basis for mAb-producing cultures and their naive counterparts. The time series were differentiated to calculate the corresponding kinetic rates (r_x = d[X]/dt; r_s = d[S]/dt; r_p = d[mAb]/dt). Results showed that these cell lines could be modeled by Monod-like kinetics if a threshold substrate concentration value of [S]_t = 0.58 g/L (for recombinant cells) and [S]_t = 0.96 g/L (for naïve cells), below which growth is not observed, was considered. A set of values for μ_max, and K_s was determined for naive and recombinant cell cultures cultured at 33 and 37 °C. The yield coefficient (Y_x/s) was observed to be a function of substrate concentration, with values in the range of 0.27–1.08 × 10⁷ cell/mL and 0.72–2.79 × 10⁶ cells/mL for naive and recombinant cultures, respectively. The kinetics of mAb production can be described by a Luedeking–Piret model (d[mAb]/dt = αd[X]/dt + β[X]) with values of α = 7.65 × 10⁻⁷ µg/cell and β = 7.68 × 10⁻⁸ µg/cell/h for cultures conducted in batch-agitated flasks and batch and instrumented bioreactors operated in batch and fed-batch mode.

Most commercial media for mammalian cell culture are designed to satisfy the amino acid requirements for cell growth, but not necessarily those for recombinant protein production. In this study, we analyze the amino acid consumption pattern in naïve and recombinant Chinese hamster ovary (CHO) cell cultures. The recombinant model we chose was a CHO-S cell line engineered to produce a monoclonal antibody. We report the cell concentration, product concentration, and amino acid concentration profiles in naïve and recombinant cell cultures growing in CD OptiCHO™ medium with or without amino acid supplementation with a commercial supplement (CHO CD EfficientFeed™ B). We quantify and discuss the amino acid demands due to cell growth and recombinant protein production during long term fed batch cultivation protocols. We confirmed that a group of five amino acids, constituting the highest mass fraction of the product, shows the highest depletion rates and could become limiting for product expression. In our experiments, alanine, a non-important mass constituent of the product, is in high demand during recombinant protein production. Evaluation of specific amino acid demands could be of great help in the design of feeding/supplementation strategies for recombinant mammalian cell cultures.

Sea cucumber body wall contains several naturally occurring bioactive components that possess health-promoting properties. Isostichopus badionotus from Yucatan, Mexico is heavily fished, but little is known about its bioactive constituents. We previously established that I. badionotus meal had potent anti-inflammatory properties in vivo. We have now screened some of its constituents for anti-inflammatory activity in vitro. Glycosaminoglycan and soluble protein preparations reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammatory responses in HaCaT cells while an ethanol extract had a limited effect. The primary glycosaminoglycan (fucosylated chondroitin sulfate; FCS) was purified and tested for anti-inflammatory activity in vivo. FCS modulated the expression of critical genes, including NF-ĸB, TNFα, iNOS, and COX-2, and attenuated inflammation and tissue damage caused by TPA in a mouse ear inflammation model. It also mitigated colonic colitis caused in mice by dextran sodium sulfate. FCS from I. badionotus of the Yucatan Peninsula thus had strong anti-inflammatory properties in vivo.

Obesity is a rising public health problem that contributes to the development of several metabolic diseases and cancer. Adipocyte precursors outside of adipose depots that expand due to overweight and obesity may have a negative impact on human health. Determining how progenitor cells acquire a preadipocyte commitment and become mature adipocytes remains a significant challenge. Over the past several years, we have learned that the establishment of cellular identity is widely influenced by changes in histone marks, which in turn modulate chromatin structure. In this regard, histone lysine demethylases (KDMs) are now emerging as key players that shape chromatin through their ability to demethylate almost all major histone methylation sites. Recent research has shown that KDMs orchestrate the chromatin landscape, which mediates the activation of adipocyte-specific genes. In addition, KDMs have functions in addition to their enzymatic activity, which are beginning to be revealed, and their dysregulation seems to be related to the development of metabolic disorders. In this review, we highlight the biological functions of KDMs that contribute to the establishment of a permissive or repressive chromatin environment during the mesenchymal stem cell transition into adipocytes. Understanding how KDMs regulate adipogenesis might prompt the development of new strategies for fighting obesity-related diseases.