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Sigma® Life Science and Axiogenesis Collaborate

Published: Wednesday, August 01, 2012
Last Updated: Wednesday, August 01, 2012
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Companies to market more predictive iPSC-based assays and services for preclinical cardiotoxicity screening.

Sigma-Aldrich® Corporation announced that Sigma Life Science, its innovative biological products and services research business, has signed an agreement with Axiogenesis to market mouse induced pluripotent stem (iPS) cell-derived cardiomyocytes and smooth muscle cells. In contrast to short-lived, tissue-derived primary cells that predominate preclinical drug discovery and cardiotoxicity screens, Sigma Life Science and Axiogenesis' iPS cell-derived primary cells enable long-term studies that are necessary to more accurately predict cardiotoxicity. These derived cell types are available as ready-to-order cells, application-specific kits and custom services catering to novice and expert users. Details are available at www.sigma.com/cardiac.

"Costly drug candidate failures in clinical trials are most frequently caused by cardiac safety issues," said John Listello, Market Segment Manager of Stem Cell Research and Regenerative Medicine at Sigma Life Science. "Early identification of these cardiac liabilities is hindered by the lack of reliable and standardized cardiomyocyte cell culture models.

"Avoiding clinical trial failures is a principle driver for the Sigma/Axiogenesis collaboration, which provides drug developers large numbers of these consistent cell culture models. This partnership deepens Sigma Life Science's commitment to alleviate critical deficiencies in ADME/Toxicology screening and preclinical development through application of iPS cell technology recently licensed from Kyoto University, CompoZr® Zinc Finger Nucleases, and the SAGEspeed(TM) Custom Animal Model Development program."

Cardiomyocytes for research and screening purposes are commonly isolated from available animal and patient tissue. The predictive utility of tissue-derived cardiomyocyte pools is limited because they do not spontaneously beat, gradually dedifferentiate into fetal-like physiological states, and contain a high percentage of contaminating cell types, such as fibroblasts that can rapidly override the culture. As a result, many critical long-term studies that could identify cardiac liabilities prior to clinical trials cannot be performed.

"In contrast, Axiogenesis' iPS cell-derived cardiomyocytes enable long-term studies that are impossible to perform in tissue-derived samples, such as accumulation studies that examine the effects of chronic dosing for several weeks at physiologically relevant, picogram levels. Accumulation patterns from such long-term studies can identify toxic compounds whose toxicity was not detectable through alternative experiments," concludes Listello.

Cardiomyocytes derived from Axiogenesis' iPS cell lines maintain physiologically-relevant biology, purity, and spontaneous beating for longer than 28 days. These iPS-cell derived cardiomyocytes are validated for functional electrophysiology, calcium-flux and calcium-wave analysis, cardiac cytotoxicity, mitochondrial metabolism, and as a disease model for cardiac hypertrophy.

Sigma Life Science's existing stem cell product portfolio includes custom iPS cell CompoZr ZFN-mediated genetic engineering, serum-free cell culture products, cell culture media, 3D matrices, growth factors, and antibodies, providing uniquely comprehensive support for iPS cell-related research. Sigma Life Science acquired a worldwide license to Kyoto University's iPS cell patent portfolio in February.


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