In our third blog on the Cellular Agriculture industry, we look at the background of cell culturing. Find out more on the ‘meaty’ topics for companies and end users, such as environmental impacts and costs.
What is cell culturing?
This is the big question – and one that is important for newcomers to the Cultivated Meat sector to understand. Cell culturing is when specific cells of interest are grown in controlled laboratory conditions. What these conditions are depends on the type of cells being grown, but some of the core components are the same: a cell culture medium is needed, which has all the essential nutrients, and the environment needs to be controlled, including variables such as temperature and pH level. Cells of all types can be grown through cell culture, with some cell lines having the ability to differentiate into multiple types of cell.
Isolation of cells
Cells can be isolated ex vivo from different tissues and animals. There are a variety of different ways to get cells, such as through blood or tissue samples, however isolating the cells from each method requires different processes.
Cell culture media
Once you have the cells, there needs to be a cell culture medium used in order to allow them to continue to grow. Cell culture media usually contains a mixture of growth factors, hormones, and other compounds which aim to regulate the cell cycle. Traditionally, the media also contains foetal bovine serum (FBS). FBS is a blood product made from foetal calves; it is used because it has a high ratio of growth factors that stimulate the cells to grow and a low level of antibodies that inhibit the cells. However, its use raises many ethical issues, and it also has a high cost.
It has been one of the key challenges to remove FBS from use for a number of reasons. Producing cell culture media without FBS helps to ensure livestock welfare, gain truly animal-free status and to keep costs down. As cultivated meat starts to be offered more widely and production is scaled up, using a medium without FBS will prove most advantageous.
At Roslin Tech, one of the benefits of our cell lines is our novel media which does not contain animal serum – the cells we produced are serum-free whilst they are grown and continually passaged. We aim to place animal welfare and sustainability at the centre of our work. By removing animal serum, our cells are truly slaughter-free whilst ensuring that cost is controlled. Additionally, developing our own media in-house allows us to tightly control the constituent components, tailoring it to our specific cell lines.
Maintaining cells in culture
Cells can be cultured in two different ways; historically, cells have been cultured in 2-D (attached to a substrate). As scaling up has become more common, more work has been done on methodologies for suspension culture (free-floating) and 3-dimensonal culturing has increased in use. There are advantages to either method – we use both in our work at Roslin Tech.
For ongoing cultivated protein production, the type of cell being maintained can play a factor. Primary cells, which are cells derived directly from a tissue or animal, are difficult to maintain for long periods of time. These cells undergo senescence naturally, which means they are not ideal as they do not grow indefinitely. Apart from tumour cells, normal primary cells have limited lifespans. They are not suitable for large scale production of cells for cultivated meat products.
One method to get cells that continually grow in cell culture is by converting primary cells into induced pluripotent stem cells (iPS cells). iPS cells, and the technology to create them, were established in 2006 by Shinya Yamanaka and his lab in Japan. They discovered and patented the use of four genes that encode for transcription factors which convert primary cells into pluripotent stem cells. This ground-breaking discovery was first completed in mice, and then swiftly applied to humans where it has been exploited in clinical applications. There has been significant interest in using the technology for the Cultivated Meat sector. However, it has only recently been applied to agricultural species such as pig and cow.
Roslin Tech’s iPS cell lines
We offer iPS cells for a range of species for research and commercial use. These are cultured serum-free and have the ability for unlimited passages. They are also validated for differentiation into a range of animal cell types, such as muscle and fat, giving broad application potential. For the cultivated meat industry in particular, the iPS cell lines allow for the production of muscle and fat components which are present in traditional meat products.
Our cells are produced with a high level of quality control. This ensures that our cells have the highest quality both in their purity and their differentiation potential. Additionally, the traceability of our cells gives peace of mind when using our cells for consumer cultivated meat product development.