Compositions and methods for increasing the culture density of a cellular biomass within a cultivation infrastructure

A method for adapting anchorage-dependent cells to suspension culture, comprising:

• a) providing anchorage-dependent cells comprising i) a nucleic acid encoding a YAP protein, operably linked to a regulatory sequence that promotes ectopic expression in the anchorage-dependent cells, or ii) a nucleic acid encoding a TAZ protein, operably linked to a regulatory sequence that promotes ectopic expression in the anchorage-dependent cells, wherein the anchorage-dependent cells are poultry or bovine fibroblast cells or poultry or bovine primary muscle-derived cells;
• b) ectopically expressing the YAP protein or the TAZ protein in the anchorage-dependent cells in a suspension culture in a cultivation infrastructure which does not comprise a substrate to which cells can adhere, wherein the suspension culture comprises agitation to prevent sedimentation and aggregation, thereby adapting the anchorage-dependent cells to suspension culture to produce suspension-adapted cells which proliferate in the suspension culture;
• c) isolating the proliferating suspension-adapted cells from the suspension culture;
• and
• d) culturing the isolated proliferating suspension-adapted cells in a second suspension culture to a density of about 105 cells/mL to about 1010 cells/mL in at least 1000 L.