Cell Sources for Cultivated Meat: Applications and Considerations throughout the Production Workflow

Abstract

Cellular agriculture is an emerging scientific discipline that leverages the existing principles behind stem cell biology, tissue engineering, and animal sciences to create agricultural products from cells in vitro. Cultivated meat, also known as clean meat or cultured meat, is a prominent subfield of cellular agriculture that possesses promising potential to alleviate the negative externalities associated with conventional meat production by producing meat in vitro instead of from slaughter. A core consideration when producing cultivated meat is cell sourcing. Specifically, developing livestock cell sources that possess the necessary proliferative capacity and differentiation potential for cultivated meat production is a key technical component that must be optimized to enable scale-up for commercial production of cultivated meat. There are several possible approaches to develop cell sources for cultivated meat production, each possessing certain advantages and disadvantages. This review will discuss the current cell sources used for cultivated meat production and remaining challenges that need to be overcome to achieve scale-up of cultivated meat for commercial production. We will also discuss cell-focused considerations in other components of the cultivated meat production workflow, namely, culture medium composition, bioreactor expansion, and biomaterial tissue scaffolding.

Bioengineering Outlook on Cultivated Meat Production

“…Three major stem cell types that have been studied for their ability to initiate CM production are mesenchymal stem cells (MSCs), fibro/adipogenic progenitors (FAPs) and satellite cells (i.e., myosatellite cells or muscle precursor cells)—SCs. When combined, these cell types have the ability to differentiate into all of the cells present in meat [ 36 ]. However, since SCs have proven to be the most promising, in the last several decades they have been used for CM experimental production, together with myoblasts [ 37 , 38 ].…”

“…When considering MSCs, it is important to emphasize they can be sourced directly from various tissues, such as the stromal–vascular fraction of skeletal muscle, bone marrow, umbilical cord, and adipose tissue [ 36 , 40 , 41 ], or by differentiating the ESCs/iPSCs [ 42 ] and further modifying them into mature myocytes, adipocytes, and fibroblasts [ 43 , 44 ]. Reprogramming of MSCs by media supplementation and specific pathway inhibitors can help overcome their poorer differentiation abilities and propagate new cell-type biogenesis and proliferation [ 45 , 46 , 47 , 48 ].…”

“…Isolation and in vitro maintenance of SCs from livestock, i.e., agriculturally important species such as cattle [ 51 , 52 , 53 , 54 , 55 ], chickens [ 56 , 57 , 58 ], sheep [ 59 ], pigs [ 57 , 60 , 61 ] and rabbits [ 54 ] have been well optimized. Additionally, for potential application in CM production, research has also been conducted with fish SCs [ 36 , 62 , 63 , 64 ]. On the other hand, protocols for obtaining skeletal myocytes [ 46 , 47 ], and SCs [ 48 ] from mouse and human PSCs have also been well optimized.…”

Agricultura celular para la producción de pescados y mariscos a base de células

“…Los músculos contienen una mezcla de tipos de células con diferentes capacidades diferenciales y de proliferación. Por lo tanto, identificar qué células utilizar para el cultivo, las proporciones de los tipos celulares para el co-cultivo y la reprogramación de las células para que puedan proliferar y diferenciarse en los tipos celulares deseados son los principales obstáculos técnicos (Reiss et al 2021). El cultivo celular ha dependido tradicionalmente del suero fetal bovino (SFB), componente costoso, insostenible e inconstante en los medios.…”

Cellular Agriculture for Production of Cell-Based Seafood

“…Muscle contains a mixture of cell types with different proliferative and differentiative capacities. Therefore, identifying which cells to use for culture, proportions of cell types for co-culture, and reprogramming of cells so that they can proliferate and differentiate into the desired cell types are the primary technical challenges (Reiss et al 2021). Cell culture has been traditionally dependent on Fetal Bovine Serum (FBS), a costly, unsustainable, and inconsistent component in media.…”