Improved Drug Screening
In Japan, ReproCELL is developing human iPSC-derived cardiomyocytes, neurons, and hepatocytes for applications in drug discovery including toxicity assays and ADME testing. “We believe iPSC technology will become mainstream in drug screening in the near future,” notes Chikafumi Yokoyama, Ph.D., CEO.
Today, immortalized cell lines are widely used in primary screening, but those cell lines lack their original functions. Primary cells, on the other hand, have diminished function, limited sources, and significant lot-to-lot variation.
ReproCELL’s iPSCs, in contrast, “combine the advantage of immortalized cell lines and primary cells, offering “infinite in vitro expansion and functional differentiated cells, so they can be supplied infinitely from pharmaceutical companies,” Dr. Yokoyama explains.
“The differentiated cells are especially suitable for second and third screenings, in hit-to-lead and lead-optimization stages where more predictable efficacy and adverse effects can be measured at mid-to-high throughput,” Dr. Yokoyama continues. The benefit is fewer animal tests and accelerated drug screening.
In the industry, one of the challenges has been to improve cell quality so iPSCs are comparable to primary cells. ReproCELL has developed iPSC-derived hepatocytes that are comparable to primary cells in terms of CYP3A4 activity. Those hepatocytes are scheduled to launch this spring.
“The differentiation efficiency is more than 90–100%. We are developing a cryopreservation system in which the activity can be maintained at a high level,” Dr. Yokoyama adds. “We have obtained positive data so far and will continue to improve the process.
“CYP3A4 is the most important enzyme for drug metabolism,” he notes. After the initial release, ReproCELL plans to release hepatocytes at six month intervals that express other specific types of enzymes.
Last October, ReproCELL launched a new product line of frozen, single cardiomyocyte cells, called ReproCardio2. “The frozen cells can be formed as a thin layer in 96-well plates for use in coded aperture imaging systems,” according to Dr. Yokoyama. “In addition, the single cells can be re-aggregated to be beating clusters, which are applied to MEA systems to measure the field potentials. Cardiotoxicity can be detected with tested compounds in both measurement methods.”