Cell Reports Sustainability (Jan 2024)

Engineered autocrine signaling eliminates muscle cell FGF2 requirements for cultured meat production

  • Andrew J. Stout,
  • Xiaoli Zhang,
  • Sophia M. Letcher,
  • Miriam L. Rittenberg,
  • Michelle Shub,
  • Kristin M. Chai,
  • Maya Kaul,
  • David L. Kaplan

Journal volume & issue
Vol. 1, no. 1
p. 100009

Abstract

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Summary: Cultivated meat (also known as cultured meat) is a promising technology that faces substantial cost barriers, which are currently driven by the price of media components. Particularly, growth factors such as fibroblast growth factor 2 (FGF2) drive the cost of serum-free media for relevant cells, including muscle satellite cells. Here, we engineered immortalized bovine satellite cells (iBSCs) for inducible expression of FGF2 and/or mutant RasG12V to overcome media growth factor requirements through autocrine signaling. Engineered cells were able to proliferate over multiple passages in FGF2-free medium, thereby eliminating the need for this costly component. Additionally, cells maintained their myogenicity, albeit with reduced myotube formation. Ultimately, this offers a proof of principle for lower-cost cultured meat production through cell line engineering. Science for society: Cultivated meat is an emerging technology that aims to produce meat through cell culture rather than conventional animal agriculture. By decoupling meat from animals, cultivated meat is projected to dramatically reduce the environmental impact of meat while simultaneously improving animal welfare and human health. To date, however, cultivated meat production is hindered by high costs, which are driven by the cell culture media. In particular, recombinant growth-promoting factors such as fibroblast growth factor 2 (FGF2) contribute a majority of the cost of these media. Here, we engineer bovine muscle stem cells to endogenously activate the growth-promoting signaling cascades that are typically triggered by exogenous FGF2, thereby eliminating the need for this costly media component. This approach offers a step toward engineering cultivated meat cells for expansion in recombinant protein-free media, an approach that would dramatically lower the cost of production.

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