Microcarriers for Upscaling Cultured Meat Production

Abstract

Due to the considerable environmental impact and the controversial animal welfare associated with industrial meat production, combined with the ever-increasing global population and demand for meat products, sustainable production alternatives are indispensable. In 2013, the world's first laboratory grown hamburger made from cultured muscle cells was developed. However, coming at a price of $300.000, and being produced manually, substantial effort is still required to reach sustainable large-scale production. One of the main challenges is scalability. Microcarriers (MCs), offering a large surface/volume ratio, are the most promising candidates for upscaling muscle cell culture. However, although many MCs have been developed for cell lines and stem cells typically used in the medical field, none have been specifically developed for muscle stem cells and meat production. This paper aims to discuss the MCs' design criteria for skeletal muscle cell proliferation and subsequently for meat production based on three scenarios: (1) MCs are serving only as a temporary substrate for cell attachment and proliferation and therefore they need to be separated from the cells at some stage of the bioprocess, (2) MCs serve as a temporary substrate for cell proliferation but are degraded or dissolved during the bioprocess, and (3) MCs are embedded in the final product and therefore need to be edible. The particularities of each of these three bioprocesses will be discussed from the perspective of MCs as well as the feasibility of a one-step bioprocess. Each scenario presents advantages and drawbacks, which are discussed in detail, nevertheless the third scenario appears to be the most promising one for a production process. Indeed, using an edible material can limit or completely eliminate dissociation/degradation/separation steps and even promote organoleptic qualities when embedded in the final product. Edible microcarriers could also be used as a temporary substrate similarly to scenarios 1 and 2, which would limit the risk of non-edible residues.

Keywords: bioprocessing; bovine myoblasts; cell expansion; clean meat; cultivated meat; microbeads; satellite cells.

Figure 1

Main steps required for production of cultured meat from an animal biopsy. A muscle biopsy is performed on a living animal. Satellite cells (SCs) are then isolated and subsequently expanded. When a sufficient quantity of cells is obtained, differentiation of SCs is induced. This includes cell fusion and myotube formation. The formed myotubes start producing proteins to form functional myocytes which can be then assembled with known food processing methods (mixing, molding) to form cultured meat (Illustrations have been taken from Servier Medical Art licensed under a Creative Commons Attribution 3.0 Unported License).

Figure 2

Main steps and molecules involved in cell adhesion to matrix. Cell surface receptors (mostly integrins) interact with specific molecules of the matrix, leading to attachment and spreading of the cell. Attachment is then enhanced through the interaction of focal adhesion (FA) proteins and integrins. Finally, a rearrangement of the cytoskeleton occurs which leads to spreading of the cell over the surface (56) (Illustrations from Goldmann et al. have been recreated with Servier Medical Art, licensed under a Creative Commons Attribution 3.0 Unported License).

Figure 3

Main variables affecting cell attachment and growth onto MCs.

Figure 4

Process requirements and variables for MC based bioprocesses in three scenarios: (1) MCs are serving as a temporary substrate for cell attachment and proliferation and therefore they need to be separated from the cells at some stage of the bioprocess, (2) MCs serve as a temporary substrate for cell proliferation but are degraded or dissolved during the bioprocess, and (3) MCs are embedded in the final product and therefore need to be edible.