It’s a pretty boring word but I make sure to include it when writing about the development of stem cell therapies, as in: “Asterias Biotherapeutics is testing an embryonic stem cell-based treatment for spinal cord injury”. It’s a key word here because no legitimate clinic would transplant embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) directly into a patient. The ability of these cells to make unlimited copies of themselves is great for growing them in the lab; but in the body, that same property presents a very real risk of tumor formation. Instead, ESCs and iPSCs are merely the base material from which specialized cells are matured from for the many promising therapies being developed for clinical trials.
To ensure safety to patients, minimizing the number of these potentially cancer-causing pluripotent stem cells still lingering in a cell therapy product is one of the main safety concerns of the Food and Drug Administration (FDA), the U.S. federal agency that approves therapies for clinical trials. So during therapy development, researchers run assays, or tests, to detect how many ESCs or iPSCs remain in their cell product and if they can form tumors.
In a paper published yesterday in Biomaterials, an Emory University research team reported on the development of a new technique that is several thousand-fold (!!!) higher in sensitivity than current assays and could be a game-changer for the quality control of stem cell-based therapies (also see an Emory U. blog about the study).
Surface-enhanced Raman Scattering Assay: it’s one in a million
In the technique, called a surface-enhanced Raman scattering (SERS) assay, gold nanoparticles are attached to proteins, called antibodies, that specifically bind to the surface of stem cells. These antibody-nanoparticles are mixed with a preparation of the cell product. A laser is then directed at the cells and a device, called a spectrometer, measures the resulting light scatter which ultimately can be converted into the number of stem cells in the cell mix.
Incredibly, this assay can detect one stem cell out of one million specialized cells making it well suited for testing clinical grade cell therapy products. In comparison, the current flow cytometry technique which uses fluorescently tagged antibodies, can spot 1 stem cell in about 1000 cells.
Another current way to detect stem cells in a cell product is through the so-called teratoma assay. In this test, a mouse is injected with the cell therapy and observed for about three months to see if any teratomas, or tumors, form from residual stem cells. While this technique is a more direct safety test, it’s very costly, time-consuming, and impractical for testing very large doses of cell therapies. As the authors mention in the publication, the SERS technique could help overcome the limitations of both the teratoma and flow cytometry assays:
“Because of their remarkable sensitivity, these SERS assays may facilitate safety assessment of cell preparations for transplantations that require a large quantity of cells, which is unachievable using flow cytometry or the teratoma assay in mice. In addition, these assays are cost-effective, easy to use, and can be done within an hour, which is much faster than the traditional teratoma assay.”
“Faster”. Now that’s a pretty exciting word I always like to include when writing about the development of stem cell therapies.