Co-Cultivation With New Glucose-Sparing Chlorella Algae Boosts Tissue Culture Efficiency by Reducing Cell Waste

Abstract

Mammalian cell culture technologies are crucial for recombinant protein production, organoid generation, medical applications, and the generation of in vitro cultivated meat. However, they are limited by high costs, lack of vascular O2-provision, and the resultant inhibition of 3D tissue formation. Effective media and nutrient usage, oxygenation, and waste management are key to improvement. Microalgae utilize organic or inorganic CO2 to produce O2 from light, which complements O2-consuming and CO2-respiring mammalian cells in culture. However, common microalgal cultivation conditions differ in temperature and salinity from mammalian cell cultivation environments, making co-cultivation short-lived and challenging. We screened several different microalgae species to identify Chlorella sp. BDH-1 (BDH-1), which has high growth rates in mammalian culture conditions, but unlike other Chlorella species, does not compete for glucose as an energy source. In co-culture, BDH-1 reduces cellular waste production by maintaining mammalian cells in oxidative phosphorylation, which stabilizes pH, tripling culture longevity, and optimizes nutrient usage, which increases growth performance up to 80%. It further allows the reduction of expensive and ethically challenging fetal bovine serum requirements. Collectively, mammalian cell/BDH-1 co-cultivation improves tissue culture health and reduces costs, paving the path for applications in the biotechnology and medical sectors.