Cell therapies get a lot of attention as a great step forward in health care, but more work in bioprocessing could make these treatments even better. “We think the upcoming wave in cell therapies will need to be defined in a functional manner to bring better products to the clinic,” says Dino Di Carlo, PhD, Armond and Elena Hairapetian Chair in Engineering and Medicine at the University of California, Los Angeles.

As Di Carlo and his colleagues pointed out, a specific approach to single-cell sorting is one way to improve cell-based therapies.

“Single-cell secretion profiling technology allows for the analysis and/or selection of individual cells based on the amount and type of secreted proteins or other bioproducts,” Di Carlo explains. “This differs from characterizing the gene expression or intracellular stores of a particular biomolecule, which may not correlate with the biomolecules that are secreted.”

To measure single-cell secretion, cells must be confined in a small volume—such as a microwell, droplet, or nanovial—where the small number of secreted biomolecules can be detected.

Key therapeutic role

The secretions of cells play a key role in these therapies. “What cells secrete are critical components of their function and directly measuring secretions provides the most confidence in obtaining a functional therapeutic product,” Di Carlo says. So, secretion-based screening could be used in many steps in developing these therapies.

As a couple of examples, Di Carlo notes that it could be used in quality control of cell therapies, because “measuring the heterogeneity in secretion response for individual cells instead of the bulk amount of secretion can better define in vivo function and rule out batches that have some outlier cells that drive response, but otherwise have poor performance.”

Plus, secretion-based screening could improve the manufacturing of cell therapies. “By selecting the most functional starting cell populations, based on the amount and type of secretions, final therapeutic products may have enhanced function,” Di Carlo says.

Technology already exists to apply secretion-based screening in commercial bioprocessing.

“The most easily accessed is Partillion Bioscience’s nanovial technology, which can be used by bioprocessors that have access to flow cytometers or single-cell sequencing technology,” Di Carlo says. “However, other instruments that are more specialized—for example, technologies from Berkeley Lights or Isoplexis—also have functionality for this application area.”

With the technology in hand, a bioprocessor can apply secretion-based screening on a commercial scale. As Di Carlo says, “Once they have these technologies, they can develop assays specific to their cell types—for example, cytokine secretion from T cells or VEGF secretion from mesenchymal stem cells—and incorporate secretion-selected cells in their workflows or define new critical quality attributes that correlate to downstream preclinical and clinical endpoints.”

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