Stem cell platform speeds up drug discovery

It doesn’t look like much, just a thin strip of muscle suspended between two fine wires. Yet this cylindrical shaped piece of cardiac tissue, no bigger than a grain of rice, is a powerful new tool for testing novel heart disease therapies.

Scientists have validated the platform with existing drugs that treat slow heart rates, chest pain, high blood pressure, heart rhythm disorders, and other conditions. Now, more and more companies are turning to this miniature version of the human heart to evaluate experimental medicines before advancing them into clinical trials.

“If you can generate data in translational models such as TARA’s that accurately reflect human biology and physiology early in the development of a drug, that should increase your speed to the market and probability of success,” says Misti Ushio, chief executive of New York-based TARA Biosystems, the company behind the heart-on-a-chip platform, named Biowire II*.

The tissues generated on the Biowire II platform are made possible thanks to the unique properties of iCell^® Cardiomyocytes², a second generation type of lab-grown heart muscle cell derived from human induced pluripotent stem cells and created by FUJIFILM Cellular Dynamics Inc.

Tens of thousands of these cells — which have been optimized for fast recovery after thawing from cryostorage — self-assemble between two wires positioned just three millimetres apart, yielding a freely suspended 3D tissue. The platform continuously delivers electrical pulses to stimulate muscle contraction bending the wires as the tissue beats.

By measuring the amount of bending in the wires, researchers can determine the force and kinetics of muscle contraction. Changes in calcium concentration and electrical patterns can also be tracked. This comprehensive view of cardiac function provides valuable data on whether or not candidate drugs would affect the mechanical properties of the human heart, which is a key indicator of heart failure.

SCREEN SAVER

Recently, researchers from TARA and GlaxoSmithKline described how heart tissue generated from FUJIFILM Cellular Dynamics cells on the Biowire II platform functioned like real, mature human heart muscle in terms of its contractile response to known pharmacological agents. The muscle tissues generated on the Biowire II platform responded to a range of drugs — both toxic and therapeutic — in ways similar to patients and animal models. The researchers reported the findings in the November 2019 issue of Toxicological Sciences¹.

According to Ushio, the decision to rely on iCell Cardiomyocytes² was strongly market-driven. Owing to the reproducibility and consistency of the product, FUJIFILM Cellular Dynamics’ cells were what drug companies had come to rely upon for their own lab-based drug screens — and as those firms moved into three-dimensional cardiac systems, they wanted to stay with the same reliable cell source.

“Almost every pharmaceutical company we interacted with said, ‘We want to work with you, but we want you to use the FUJIFILM Cellular Dynamics cells, because if you can really recapitulate the biology using these cells that we use every day, that will be meaningful.’”

The proven performance of the cells — with their stable biological profiles and recovery from cryopreservation — also made partnering with FUJIFILM Cellular Dynamics an obvious choice, says Ushio. “Their consistency helps with our consistency,” she says. “It expands what we can do because we have a reliable starting point as a foundation.”

ASSAY DEVELOPMENT

Well over a dozen other companies similarly use FUJIFILM Cellular Dynamics’ cells in their drug-screening assays. For example, at StemBioSys in San Antonio, Texas, scientists grow iCell derivatives — currently cardiomyocytes and expanding to other cell types — on biological substrates (CELLvo™ Matrix) that aim to recapitulate biochemical as well as structural and mechanical cues of the native niche thus creating a biologically relevant culture environment. The cells on this matrix then develop together with polarized morphology, alignment and other biophysical properties, allowing researchers to accurately determine whether drug compounds will prove harmful to the heart, brain or liver.

And although the name on the final assay that allows for this kind of predictive drug screening is rarely FUJIFILM Cellular Dynamics’, a dedicated team of scientists from the Wisconsin-based Fujifilm subsidiary has usually had a hand in helping partner firms make the most of what iPSC-derived products have to offer.

“People see us as a cell provider, but one of our greatest strengths is in assay development and creating cell analysis platforms that will translate into the clinic,” says Eugenia Jones, vice president of the life sciences strategy office at FUJIFILM Cellular Dynamics.

Working with iPSCs and their differentiated progeny is not easy. The highly specialized cells require controlled culture conditions for optimal maintenance and performance. Get any of the culturing methods, growth media, or nutrient feeds incorrect and the in vitro platform will no longer accurately reflect in vivo biology.

That is why many academics and companies that focus on drug discovery platforms choose to work with FUJIFILM Cellular Dynamics, notes Jones. Simply put: “We help people work with the cells,” she says.

If any assay providers are interested in using high quality and reliable iPSCs to accelerate their drug discovery efforts, Jones offers this simple advice: “Come to us if we have the right cell type for you and you want help getting it into a screen faster.”

_{* BIOWIRE is a trademark of TARA Biosystems, Inc. in various jurisdictions.}