Dr. Petra Hanga is working to optimize cell-based meat production by creating a robust and reliable scale-up process for fat and muscle cells. With funding through GFI’s Competitive Research Grant program, she and her team are exploring techniques to achieve the quantity of cells and complexity of structure needed to produce meat without animal agriculture.
In an interview with Dr. Hanga, we spoke all things cell culture: the difference between fat and tissue, the cost of cell-culture media, and why the UK is the perfect place for research.
What challenges does your research project address?
We are addressing two of the main challenges currently hindering the commercialization of cell-based meat. The first is the large numbers of cells required for cell-based meat. The second challenge is the complexity of the meat which gives beef its texture, taste, and nutritional value. Our project will produce large quantities of fat and muscle cells to address these issues. The process is done in culture vessels (called bioreactors or cultivators) capable of precisely controlling the conditions like temperature, pH, and gases while maintaining a sterile environment. Fat and muscle cells will then be combined in different proportions. The cells form microtissues to biomimic conventionally produced meat.
How did your background in biological engineering lead you to cell-based meat research?
I only recently discovered my interest in cell-based meat. I am an animal lover and an empathetic person. The idea that we can enjoy meat without having to slaughter animals for our own benefit is highly appealing to me. The more I read about the potential benefits of cell-based meat over industrial animal agriculture, the more I am interested in and excited about the future.
I am a biochemical engineer by training, with a PhD in Regenerative Medicine. I specialized in the bioprocessing of stem cells and joined Professor Chris Hewitt’s group. With his support and mentorship, I started as an independent academic. I began manufacturing cell-based therapy in stem cells. I came to realize that the field is multidisciplinary, as people must understand both engineering and biology. My knowledge is directly applicable to cell-based meat and I want to use my talents to improve the meat industry.
What unique resources exist in the UK to benefit cell-based meat research?
I strongly believe that the UK is uniquely fit to contribute to research with its world-wide biological manufacturing. Even so, the concept of cell-based meat is new to the UK. Only recently have several start-up companies formed. I expect this to expand in the future.
Our group is well established and internationally renowned in the field of stem cell bioprocessing. We understand the whole cell culture process from inoculation (introducing cells to media) to cell harvest. Our expertise is directly relevant to cell-based meat.
What are the major differences between adipogenic and myogenic lineages? Why does this matter for cell-based meat?
Meat has a complex structure. It is composed of multiple different cell types. These give meat its texture, taste, and nutritional value. One cell type alone would not be sufficient to replicate farm-produced meat. This challenge can be overcome by co-culturing two different types of cells: fat, which is an adipogenic lineage and muscle, a myogenic lineage.
The two cell types are fundamentally different. We anticipate that they will need to be produced separately in bioprocesses customized to the cell type. Different requirements exist to transform mesenchymal stem cells (an early stage in cell differentiation) into adipogenic and myogenic lineages. They need different molecules, feeding regimes, cell densities, and agitation rates in bioreactors. Only after we culture both types of cells can we create cell-based meat.
What is cell encapsulation technology, and how does it relate to your research?
Cell encapsulation is a technique that uses hydrogels to entrap cells inside them. Hydrogels are polymer gels that can absorb and retain large amounts of water. They are semi-permeable, meaning that nutrients and waste products can pass through while gas is exchanged with the environment. A common example of a hydrogel is gelatin, which is animal-based. We will be experimenting with non-animal-based hydrogels. In our project, the encapsulation technology is used to provide support for co-culturing two different cell types (fat and muscle). It allows us to promote interactions between fat and muscle cells, and remodel both into microtissues.
What is currently the costliest stage of the scale-up bioprocess, and why?
In our experience with human stem cells, the distribution of costs depends on a series of factors. Some significant ones are the types of media (serum-free vs. serum-based) and bioreactors (single-use vs. reusable). Serum-free media and single-use bioreactors are more expensive but have notable advantages. For example, serum-free media results in higher cell densities.
Typically, higher costs are associated with larger volumes of media. For our project, two types of media are needed which complicates the story. The first (growth media) is relatively cheap, though the second (differentiation media) is expensive. The former is used for growing large numbers of mesenchymal stem cells, and the second for initiating differentiation between fat or muscle cells. The benefits might outweigh the cost in the end.
Which stages of the process do you expect to be the most successful and most challenging in reducing costs?
The most challenging step is differentiating the lineages with great efficiency. It requires a specific form of media that is highly-priced on the commercial market, and the process itself is lengthy. The process lasts up to 21 days, meaning that we will require a large volume of media.
On the positive side, we hope to optimize the process of expanding mesenchymal stem cells in bioreactors. This will reduce the costs of bioprocessing significantly. We will maximize the number of cells in culture. If we can achieve a high cell yield, our approach will result in a more cost-effective process.
Check out all fourteen research grant proposals! For a deeper dive, GFI senior scientist Dr. Erin Rees Clayton contextualizes the plant-based and cell-based meat projects within current industry challenges.