New continuous cell therapy bioprocess

Article by Neil Clark

A COATING that allows the first ever continuous production of cells could remove a significant bottleneck in the production of cell-based therapies, according to researchers.

Connon said: "Remarkably, with this continuous production technique even a culture surface the size of a penny can, over a period of time, generate the same number of cells as a much larger-sized flask."

The team, from the University of Newcastle, UK, says their surface coating removes the limit on the number of cells that can be grown in a culture dish, which until now has been strictly confined by its surface area. This would save costs, reduce materials and improve the quality of products to treat heart, cartilage, skin and cancer-related diseases.

While current methods of production require batch culture, where cells are chemically or enzymatically removed all at once after growth, the new coating allows cells to continuously self-detach for collection. As a result, further cells can grow in their place.

“This allows us to move away, for the first time, from the batch production of cells to an unremitting process,” said Che Connon, professor of tissue engineering at Newcastle, adding: “With our new technology, 1 m2 would produce enough cells to treat 4,000 patients, while traditional methods would require an area equivalent to a football pitch.”

The coating is made from peptide amphiphiles, which are molecules based on small chains of amino acids. This class of materials combines the structural features of amphiphilic surfactants with the functions of bioactive peptides, and are known to assemble into a variety of nanostructures.

The team’s coating works by providing a cell binding site above an amino acid sequence that is sensitive to a class of enzymes called matrix metalloproteinases (MMPs). Cells to be grown produce MMPs as they grow, which facilitates their release. The rate of cell detachment can be controlled by adding retinoic acid, which changes the rate at which cells produce MMPs.

In a ACS Applied Materials & Interfaces paper, use of the coating was demonstrated to result in a ~1% recovery of the total attached cells per hour, which was maintained over a month.

“Our new technology also offers complete control over the rate of cell production, so it could be scaled up using existing stacked culture flasks to produce 1bn cells per week, or scaled down so as to fit a bioreactor on the head of a pin,” Connon said.

While continuous, bioprocessing is currently used to produce biopharmaceuticals like vaccines and anti-cancer antibodies, it has never been achieved for cellular therapies. Such treatments, which include stem cell therapies, can require up to a billion cells per patient – and there are, for example, an estimated 10m annual patients who could benefit from cardiac cell therapy.

Connon told The Chemical Engineer that the main challenge now facing the development of his technology is its radical nature. “Systems have been set up for batch culture for the last 50 years,” he said, adding: “We are now looking for commercial partners to co-develop this technology. This could be in cell-therapy or any business requiring lots of cells – for example, Memphis Meats (a food technology company growing cultured meat) could be an interesting partner.”

ACS Applied Materials & Interfaces:

Article by Neil Clark

Staff Reporter, The Chemical Engineer

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