Although the idea of growing meat in a laboratory may seem like science fiction, over a decade has passed since the first synthetic beef burger was unveiled in 2013 (Kupferschmidt, 2013). Moreover, in June 2023, two companies – Upside Foods and GOOD Meat – were granted approval by the Food and Drug Administration (FDA) to sell ‘cultured meat’ products in the United States (Wiener-Bronner, 2023).
While producing meat in a laboratory could eventually lead to a reduction in livestock farming, which would bring benefits in terms of improved animal welfare and reduced environmental impact (Post, 2012), the process is not free from challenges. For instance, there are concerns around food safety, the high cost of production, and whether the public will accept meat that has been artificially made. Also, if the cultured meat does not taste exactly like the real deal, consumers may turn away. Moreover, cultured meat products will have to compete against other, more affordable options, such as plant-based burgers.
A compelling advantage of cultured meat is that its texture, flavor and nutritional content can be tailored during production (Broucke et al., 2023). Lab-grown meat is made by isolating cells from the tissue of a live animal or fertilized egg, and differentiating them into muscle, fat and connective tissue. By altering the composition of cells generated during this process, researchers could make lab-grown meat that is personalized to an individual’s taste. However, combining and co-culturing the different source cells needed to produce these three components is no easy task. Now, in eLife, Hen Wang and co-workers – including Tongtong Ma, Ruimin Ren and Jianqi Lv as joint first authors – report an innovative approach for customizing cultured meat using just fibroblasts from chickens (Ma et al., 2024; Figure 1).
First, fibroblasts were sourced from the fertilized eggs of chickens and grown on a flat surface. The cells were then implanted into a three-dimensional scaffold made up of hydrogel (grey cylinder …
First, the team (who are based at Shandong Agricultural University and Huazhong Agricultural University) optimized the culture conditions for the chicken fibroblasts. This included changing the composition of the medium the cells were fed, and developing a three-dimensional environment, made of a substance called hydrogel, that the fibroblasts could grow and differentiate in. Ma et al. then used a previously established protocol to activate the gene for a protein called MyoD, which induces fibroblasts to transform into muscle cells (Ren et al., 2022). Importantly, the resulting muscle cells exhibited characteristics of healthy muscle cells and were distinct from muscle cells that appear during injury.
While muscle is a fundamental component of meat, the inclusion of fat and extracellular matrix proteins is essential for enhancing flavor and texture (Fraeye et al., 2020). To stimulate the formation of fat deposits between the muscle cells, the differentiated chicken muscle cells were exposed to fatty acids and insulin. This caused the cells to produce lipid droplets, signifying that the process of fat synthesis had been initiated. Measuring the level of the lipid triglyceride revealed that the fat content of the cultured fibroblasts was comparable to that in real chicken meat, and even climbed two to three times higher when insulin levels were increased.
Ma et al. then validated that the chicken fibroblasts were also able to produce various extracellular matrix proteins found in connective tissue. This is critical for forming edible cultured meat products as the tissue surrounding muscle cells gives meat its texture and structural integrity.
The study by Ma et al. underscores the potential for modulating key components (such as muscle, fat, and extracellular matrix proteins) to produce high quality lab-grown meat that is palatable to consumers. It also demonstrates how the important components of meat can be produced from just a single source of fibroblasts, rather than mixing multiple cell types together. As this is a proof-of-concept study, many of the issues associated with producing cultured meat for a mass market still persist. These include the high cost of components such as insulin, and concerns around the use of genetically modified cells: moreover, potentially toxic chemicals are required to activate the gene for MyoD.
Nevertheless, advancements in biotechnology, coupled with the recent FDA approval for genetically modified cells in lab-grown meat production (Martins et al., 2024), signal a promising future for the cultured-meat market. In the future, genetic, chemical and physical interventions may be used to precisely design other bioactive compounds found in meat, in addition to fat and muscle (Jairath et al., 2024). It may not be long until personalized cultured meat products with finely-tuned flavors, textures, and nutrients are available for sale.
© 2024, Jin and Bao
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The endothelial blood-brain barrier (BBB) strictly controls immune cell trafficking into the central nervous system (CNS). In neuroinflammatory diseases such as multiple sclerosis, this tight control is, however, disturbed, leading to immune cell infiltration into the CNS. The development of in vitro models of the BBB combined with microfluidic devices has advanced our understanding of the cellular and molecular mechanisms mediating the multistep T-cell extravasation across the BBB. A major bottleneck of these in vitro studies is the absence of a robust and automated pipeline suitable for analyzing and quantifying the sequential interaction steps of different immune cell subsets with the BBB under physiological flow in vitro. Here, we present the under-flow migration tracker (UFMTrack) framework for studying immune cell interactions with endothelial monolayers under physiological flow. We then showcase a pipeline built based on it to study the entire multistep extravasation cascade of immune cells across brain microvascular endothelial cells under physiological flow in vitro. UFMTrack achieves 90% track reconstruction efficiency and allows for scaling due to the reduction of the analysis cost and by eliminating experimenter bias. This allowed for an in-depth analysis of all behavioral regimes involved in the multistep immune cell extravasation cascade. The study summarizes how UFMTrack can be employed to delineate the interactions of CD4+ and CD8+ T cells with the BBB under physiological flow. We also demonstrate its applicability to the other BBB models, showcasing broader applicability of the developed framework to a range of immune cell-endothelial monolayer interaction studies. The UFMTrack framework along with the generated datasets is publicly available in the corresponding repositories.
We investigated the role of the nucleolar protein Treacle in organizing and regulating the nucleolus in human cells. Our results support Treacle’s ability to form liquid-like phase condensates through electrostatic interactions among molecules. The formation of these biomolecular condensates is crucial for segregating nucleolar fibrillar centers from the dense fibrillar component and ensuring high levels of ribosomal RNA (rRNA) gene transcription and accurate rRNA processing. Both the central and C-terminal domains of Treacle are required to form liquid-like condensates. The initiation of phase separation is attributed to the C-terminal domain. The central domain is characterized by repeated stretches of alternatively charged amino acid residues and is vital for condensate stability. Overexpression of mutant forms of Treacle that cannot form liquid-like phase condensates compromises the assembly of fibrillar centers, suppressing rRNA gene transcription and disrupting rRNA processing. These mutant forms also fail to recruit DNA topoisomerase II binding protein 1 (TOPBP1), suppressing the DNA damage response in the nucleolus.