NEW YORK (GenomeWeb) – While cancer stem cells (CSCs) — subpopulations of cells within a tumor that are capable of driving the disease — have become a promising subject of research, their scarcity and the complexity associated with their isolation has made their use in drug screening difficult.
But a new method developed by a team from the University of Florida, Gainesville promises to overcome this hurdle, enabling the delivery of small-molecule drugs to individual islands of rare patient-derived cancer cells on a miniaturized microarray platform.
Traditional drug screening requires large quantities of cells, which is problematic for studies involving rare cells. Although technological advances have led to the creation of cell-based microarrays that require substantially less cellular input, these have their own shortcomings.
Many of these newer approaches rely on immobilizing target molecules, which limits their applicability to small-molecule drug libraries, the UF team wrote in a paper appearing in the Proceedings of the National Academy of Sciences. Others, meanwhile, rely on robotically spotting cells, a technique "not amenable to widespread adoption."
Array platforms that can capture single cells are becoming more available, but the determination of chemotherapeutic efficacy is better investigated with methods that use greater cell numbers, which better capture variability in cellular responses, the researchers stated. "Furthermore, arrays of drug-loaded polymer films with an overlying cell monolayer have been developed, but monolayers of cells are susceptible to [cell-to-cell] signaling, which are particularly important for multipotent cells."
To address the issue, the scientists developed drug-eluting microarrays comprising a non-fouling polyethylene glycol background onto which hundreds of isolated drug-loaded polymer islands are spotted. The islands act as drug depots that co-localize with adherent cells to create isolated culture environments.
"The use of programmable arraying techniques can then enable fabrication of uniquely formulated drug-eluting spots that provide prescribed drug doses and drug combinations to overlying cells for simultaneous testing on a single device," they wrote in PNAS.
The researchers demonstrated their platform by constructing and testing combinatorial chemotherapeutic drug-eluting microarrays, finding that they could obtain significant results with fewer than six percent of the cells required for a typical 96-well plate. They demonstrated reliability by an average coefficient of variation of 14 percent between all of the microarrays and 13 percent between identical conditions within a single microarray.
Using the drug-eluting array with rare colorectal CSCs from two different patients revealed exhibited unique responses to drug combinations between cell sets, highlighting the potential of the platform as a prognostic tool to identify personalized chemotherapeutic regimens, the study's authors added.
Overall, this novel microarray represents an "enabling diagnostic tool for academic and clinical laboratories targeted CSC populations to define chemotherapeutic treatment options," they concluded.