Two new methods have been developed to test the health and potency of cells grown in a lab for use in some stem-cell treatments, which could lead to far more effective prediction of potency for clinical trials.
Previously, tests examined only single molecules. There was no assay, or testing procedure, available to check how effective large numbers of cells were after they were extracted from a patient and manipulated to treat certain conditions, like inflammation, according to research from the Galipeau lab at the Program for Advanced Cell Therapy (PACT) at the UW School of Medicine and Public Health
The research was recently published online in the open-access journal Cell Reports.
In this type of treatment, once the cells are manipulated, they are reinjected into a patient and the body’s immune system takes over and uses the new cells to attack the cells causing the disease.
Jacques Galipeau, MD, professor of oncology and PACT director, and his colleagues are examining the use of mesenchymal stromal cells for treatment of inflammatory diseases such as Crohn’s disease and graft vs. host disease. Their work, in part, was spurred by why past clinical trials on the use of stem-cell treatments for inflammatory conditions failed. Galipeau is the senior author on the paper.
The reasons the trials failed came down to potency, according to Raghavan Chinnadurai, assistant scientist in the Galipeau lab and lead author.
“In one case, they would extract the cells, alter them to fight the condition, grow more, freeze them and then ship them across the country,” he said. “When the cells arrived, they were not as healthy as when they were grown, and the trial failed because of it.”
There was no way to test how strong the cells were, until now, Raghavan said.
The other concern is identifying the point at which growing cells in the lab start to become less healthy and effective.
To establish the potency of mesenchymal stromal cells, Raghavan and his team created two assays that test the potency of the cells using two different methods.
One, called a secretome-based assay, measures how the mesenchymal cells respond to immune blood cells called peripheral blood mononuclear cells.
The other test is a transcriptome-based assay that measures the expression of RNA genes when the mesenchymal cells interact with nearby peripheral blood mononuclear cells or a signalling protein called interferon-gamma.
In both assays, the guiding principles are to compare resting mesenchymal stromal cells with their activated counterparts (extracted and manipulated mesenchymal cells) and rigorously correlate secretome and transcriptome response with the suppression of the peripheral mononuclear blood cells’ reproduction, according to the paper.
These assay systems can guide FDA-compliant development of mesenchymal stromal cell therapies worldwide, Raghavan said.
“Nobody has shown this kind of approach,” he said.