![]() One commonly used method to bypass activation of anoikis in suspension-based bioreactors is through the use of microcarriers. As discussed in Bioprocessing, this non-native environment can lead to anoikis if cells are not adapted to suspension growth, grown as spheroids, or otherwise tricked into anchorage independence via small molecules such as Rho Kinase (ROCK) inhibitors. Microcarriersĭuring the proliferation phase, anchorage-dependent stem cells are to be grown in bioreactors at large scales. This biology, together with changes in the cell culture medium composition, will assist in driving the future creation of structured, 3D cultivated meat products. By mimicking in vitro the ECM stiffness and protein composition of a specified stem cell niche microenvironment, stem cells can be guided into predictable lineages. The importance of ECM proteins for myogenic differentiation has also been demonstrated in primary cultures from mussel ( Dyachuk 2013 Odintsova et al. Over the last two decades, a large set of studies have demonstrated the critical role of the ECM in the regulation of stemness and differentiation across all of the relevant cell types for cultivated meat production: pluripotent stem cells (Wang et al., 2015), mesenchymal stem cells (Engler et al., 2006), satellite cells (Calve et al., 2010), and adipogenic stem cells (Guneta et al., 2016). Indeed, the regulation and maintenance of stem cells in the adult body is highly dependent on the ECM components that make up the stem cell niche, where each tissue’s niche typically contains a unique set of ECM components (Gattazzo et al., 2014). Because components of the early embryo are all stem cells, this means that stem cells are exquisitely sensitive to ECM cues. In essence, as cells become defined, their gene expression patterns dictate the creation and secretion of specified ECM components, which in turn act as a feedback mechanism to further dictate cellular differentiation and migration, a process referred to as “dynamic reciprocity” (Bissell et al., 1982). Additional factors such as ECM density and gradients, composition, and 3D topography can have large effects on cell behaviors (Rozario and DeSimone, 2010). During this time, ECM components and cells themselves are actively in motion as they pass through key developmental landmarks such as the formation of the primitive streak, gastrulation, and tissue specialization (Loganathan et al., 2016). differentiate) in part via cues from their extracellular environment. Altogether, this process is referred to as mechanotransduction (Figure 1).ĭuring embryogenesis and development, cells multiply and become specialized (i.e. These connections collectively mediate a cell’s ability to sense the extracellular environment, leading to downstream signaling that can affect cell polarity, migration, and differentiation ( Handorf et al., 2015 Sun et al., 2016) Dyachuk 2013 Odintsova et al. The integrin-mediated focal adhesion can be thought of as the midpoint of a tug-of-war between the ECM and a cell’s internal cytoskeleton. Integrins act as mechanosensors to mediate downstream effector proteins, leading to the formation of focal adhesion complexes that connect the actomyosin cytoskeleton to the extracellular matrix. The ECM has an inherent stiffness that in turn can influence cellular activity via specialized cell membrane proteins called integrins. In vivo, cells exist within a complex matrix of secreted proteins and proteoglycans called the extracellular matrix (ECM). ![]() How are trillions of stem cells then turned into structured meat via differentiation? In order to understand, background on the extracellular matrix and mechanotransduction is necessary (Ahmad et al. The initial proliferation of stem cells is an essential part of the cultivated meat production process. The extracellular matrix and mechanotransduction A review of the core bioengineering biology, scaffolding technologies, and methods to consider for the creation of complex structures are discussed below. In order to replicate the more sophisticated products, scientists will need to borrow and improve upon technologies from tissue engineering, regenerative medicine, and biomaterials science to recreate the complex multicellular architecture of meat. On one end of the spectrum, there are less sophisticated processed products such as surimi and hot dogs in the middle, minced products such as burgers and sausages and on the other end, filets and steaks. The range of meat products on the market exists on a spectrum of structural sophistication.
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