Project Lead(s): Peter Zandstra
Counterfeit and substandard drugs are increasingly present in developing nations.
In many low- and middle-income countries (LMICs), drug quality is tested by the thin-layer chromatography (TLC) test, which compares a sample’s composition to compositions published when the drug was first registered with the FDA.
However, this test cannot identify any compounds that are not normally present when the drug is produced, including harmful contaminants that can arise if the drug is improperly made or counterfeit.
Pharmaceutical companies have started to test for drug safety in vitro with pluripotent stem cell- (PSC) based assays, but their high production cost precludes their use in LMICs.
The project team proposed to develop a device that would enable low-cost drug screening of drugs using human pluripotent stem cell- (hPSC) based cardiac function.
Costs of using PSCs for screening are usually driven up by the high production cost of hPSCs, as each drug test usually requires up to $10,000 of hPSC growth media to produce the necessary hPSCs for screening.
The team sought to develop an economical, scalable bioreactor to generate relevant numbers of hPSCs and hPSC-derived cardiomyocytes (CM) and to use the hPSC-derived CM to develop cardiac micro tissues in a configuration that would allow for quantification of contractile force exerted by the CM in the presence of different drug conditions.
The device design consisted of a 96-well plate and, within each well, there were, pins around which CM and fibroblasts were seeded to form a “microwire”. The deflection of the pins would permit calculation of the contractile force exerted by the cardiac microtissue.
Progress was made in scale-up and production of the required cell types and a prototype device was successfully developed for drug screening. However, the team was unable to make this cost-effective during the grant period.
As such, the team was significantly delayed in initiating drug screening with collaborators in Ghana and did not establish the technology in a developing country.
The team is continuing to develop its bioreactor for hPSC expansion, aiming to increase yield on a per-cost basis.
To that end, they are developing a robust screening experiment for identifying and mitigating sources of variability in the cell growth technique, which will significantly enhance the application of the expansion system.