3D differentiation conditions for the production of cultured meat from livestock stem cells

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Global demand for meat is steadily increasing (3%/year), and is further exacerbated by population growth, which is estimated to reach 10 billion by 2050. Livestock meat production uses ~70% of global arable land, contributes to increases in greenhouse gases (beef) and considerable water use. Based on the anticipated increase in global demand we will have insufficient planetary resources to provide meat to the world population by the middle of the century. Thus, alternative methods for the production of nutritious, palatable and sustainable meat are urgently needed. The cellular agriculture sector has recently emerged as a possible solution to the production of meat in the laboratory, however bioengineering solutions for the production of cultured meat are still in their infancy. In this project we will take advantage of our complementary expertise in stem cell biology (RA), biomaterials/matrix biology (CM) and synthetic chemistry (NRT) to develop a technologically innovative approach to the production of cultured meat. Meat is a complex tissue, with muscle cells representing the main cellular component, and complemented with smaller proportions of adipose and connective tissue. Developing methods for producing muscle cells that recapitulate the organisation of skeletal muscle in vitro is the foundation for the creation of an alternative source of meat that could then be further engineered to contain other cell types and deliver a nutritious and palatable product. We will test the hypothesis that modulation of the extracellular environment can have a positive effect on muscle and fat cell fate specification.During embryonic development, tissue specification is the result of a complex interplay between cells and the extracellular matrix (ECM) that surrounds them. That matrix is composed of proteins and glycans that exist in different forms, the exact combination of which gives each tissue unique characteristics with regard to both mechanical and biochemical properties. Cells respond to these signals as they form specialised tissues such as muscle and fat, often re-modelling the matrix as they do so. In vitro, stem cell differentiation has traditionally made use of the animal derived matrix preparation, Matrigel. However, this product has significant limitations including a lack of reproducibility, the intractable complexity of the material and the 3Rs limitations when trying to create an animal-component free product. Using a peptide hydrogel previously optimised by our group for culture of mouse and human pluripotent stem cells, we can selectively introduce matrix components to test the impact these have on the differentiation of animal stem cells to muscle and fat. Importantly, the addition of matrix proteins or glycans can be carried out independently to altering the mechanical properties of the hydrogel, allowing separate evaluation of the impact of both of these critical factors.