In an exclusive interview with GEN, Sakis Mantalaris, PhD, professor of biomedical systems engineering at the Georgia Institute of Technology, explained that identifying metabolic biomarkers could help cell therapy developers speed up and optimize their manufacturing processes.

“If you identify and use biomarkers then, as we’ve shown in theory and to some extent in practice, you can have a very fast bioprocess,” he said.

Mantalaris, who gave a talk at the Bioprocessing Summit, pointed out that he has shown that cell metabolism changes more dynamically than protein or gene expression during bioprocessing.

In a scientific report, he and a team exposed embryonic and induced pluripotent stem cells to a Rho-kinases (ROCK) Inhibitors, a common technique for improving human embryo stem cell survival in culture.

“In the literature, people had noticed no changes in gene and protein expression, so the question we asked is does metabolism change,” he continued.

Rapre GEN Figure Bioprocess
The bioprocess (I), generating metabolomics signatures of input cell, the bioprocess, and the output cells (II), and the metabolomics results comparing differentiation protocols with the golden standard primary cells (III). [Sakis Mantalaris, PhD]
The team found that metabolism was clearly changing within 12 hours, the earliest time point they studied, and was changed until 96 hours to a final metabolic state. In another study on mesenchymal stem cells, they found monitoring metabolic state gave more consistent results than measuring traditional gene and protein expression.

From his studies and others, he argues that manufacturers could monitor the state of cells more accurately by monitoring metabolomics during bioprocesses. Going further, he adds, they could even deliberately alter metabolism to modulate cell functions and “reprogram the cells.”

Asked why the cell therapy sector was lagging behind manufacturers of monoclonal antibodies, and other biologics, he said: “It’s a newer industry. It’s not been through the same long curve of regulatory applications and bioproduction standardisation compared to biologics.”

He added that proteomics, genomics, and metabolomics were all new technologies, and cell therapy manufacturers had turned first to traditional tools.

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