Multi-Organ Approaches to Cultivated Meat Biomanufacturing: Conceptual Applications of Ruminal Fermentation and Co-Cultures.

Current academic research and industrial processes for cultivated meat production primarily utilize cultures of single cell types (monocultures) that do not capture the complexity of the in vivo environment of muscle and fatty tissues in the body. These systems are simplified for operational practicalities and cost reduction rather than to improve product quality. Irrespective of the manufacturing process, a food product must be of high quality to survive in competitive markets. Co-culture of multiple cell types is a well-established practice that enhances tissue qualities by allowing the cells to exchange cytokines and nutrients and to engage in cell-cell signaling. These synergies promote tissue function and phenotype stability and alter cellular and tissue composition. Co-culture can improve processes by reducing the need for exogenous media components such as growth factors. Expanding this system to include the products of rumen fermentation, such as B-vitamins and short-chain fatty acid (SCFA) has potential to further improve culture conditions and product qualities, particularly for cultivated meat of ruminant species (e.g., cattle, goats, sheep, and lambs). In this review, we cover the role of multiple cell types (notably fibroblasts and liver cells) as well as the role of rumen fermentation products in supporting the development and quality of the desired muscle and fatty tissues. We identify the opportunities and highlight the challenges associated with connecting these cultures as modules in a multi-organ bioreactor series to further enable synergies and improve product qualities as part of a novel, bio-inspired, multi-organ production system.