GE Healthcare and Geron announced this week that they are partnering to offer human embryonic stem cell (hESC)-derived assays for drug development and screening toxicity (see page 2). HESC-derived cell-based assays promise to supplement in vivo animal and in vitro cell testing for drug development. Applications could include target identification and validation, screening of compound efficacy and safety-assessment studies.

Konstantin Fiedler, GE Healthcare’s Cell Technologies general manager, told the Wall Street Journal that he expects the hESC-derived toxicity testing market to total in the low hundreds of millions of dollars by 2020. As part of its partnership with Geron, GE will utilize its cell manufacturing abilities through its Cell Factory outsourcing service. “GE Healthcare’s Cell Factory increases the capability and capacity of researchers who use cell-based assays for high-throughput and high-content screening,” said Conor McKechnie, International PR manager at GE Healthcare, to IBO. “Single batches of cryopreserved cells can be produced in quantities sufficient for complete screening campaigns, effectively decoupling cell production from screening in drug discovery applications,” he continued. Although the partnership with Geron is GE’s first foray in the stem cell market, the venture fits neatly with the Cell Factory business model. “With cell-based screening now playing a role in all stages of drug R&D, a reliable, consistent and plentiful supply of cells is critical if shortages of cell assays are not to become a significant bottleneck. GE Healthcare’s Cell Factory provides researchers with ready-grown frozen cellular assays for drug screening.”

Mr. McKechnie told IBO that the initial agreement between the companies will run for two years. Unlike GE, Geron has worked with hESC-derived cells for many years. In 2007, the company announced proof of principle for its hESC-derived liver cells (hepatocytes) and patented methods of drug screening using hepatocyte cells differentiated from hESCs. Geron’s main business is the development and commercialization of stem cell–based therapies.

All mature human cell types may be derived from hESCs. HESCs are also capable of providing a reliable, unlimited and physiologically relevant source of cell-based assays for drug development. In addition, hESCs allow for better control of cell phenotype and genetic characteristics. GE and Geron plan to initially release assays based on hESC-derived heart cells (cardiomyocytes) and hepatocytes, according to the Financial Times. Cardio- and hepatotoxicity account for most adverse drug effects. To test for these effects, in vitro studies using primary and transformed cells, as well as in vivo animal testing are currently employed. However, transformed cells may not properly duplicate the phenotypes and mechanisms normally observed in unmodified cells. While in vitro testing with primary cells provides a more biologically relevant model to predict toxicology, supplies are problematic and cells vary from batch to batch. In vivo animal tests are expensive and raise ethical concerns. In addition, they do not adequately simulate human physiology.

One application of hESC-derived cell assays may be the study QT interval prolongation, a form of cardiotoxicity. Specifically, the ion channels of hESC cardiomyocytes have been shown to provide a more effective model for such research than transformed cells. Likewise, HESC hepatocytes could provide a more useful model for studies of drug metabolism, as hepatocytes from primary cells quickly lose metabolic functions when used in vitro. Also, cell lines currently used for toxicity testing have low levels of metabolizing enzymes.

Although GE and Geron’s partnership promises a fast turnaround for commercialization, they are not alone in this field. Cellartis recently renewed its 2006 agreement with Astra Zeneca to develop screening assays using hESC-derived hepatocytes and cardiomyocytes. In early 2008, Cellartis also formed a partnership with Pfizer for the development of hESC-derived drug discovery tools. In 2008, Cellular Dynamics International partnered with Roche to develop and test new drug discovery models using hESC-derived cardiomyocytes. VistaGen Therapeutics last year received nearly $1 million from the California Institute for Regenerative Medicine for hepatocyte research for toxicity assays. GlaxoSmithKline, AstraZeneca, Roche and the UK government formed the Stem Cells for Safer Medicines consortium in 2007 to support hESC-derived hepatocyte and cardiomyocyte research for use in high-throughput toxicology screening.