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CDI Scientists Report on Efficient Method to Produce Footprint-Free iPSCs Under Feeder-Free Conditions

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Cellular Dynamics International, has announced the publication of research demonstrating an efficient and scalable method of creating DNA integration-free, or footprint-free, induced pluripotent stem cells (iPSCs) under a feeder-free condition using chemically defined media. This method, published on March 1 in PLoS ONE, will likely be valuable for the production of clinical-grade human iPSCs.

Junying Yu, Senior Director, Advanced Development Programs, and lead author of the paper, and her colleagues at CDI improved efficiency over her previously published method that resulted in exogenous DNA-free iPSCs by employing a cocktail containing four small molecules and cultured in chemically defined media free of feeder cells.

The addition of small molecules significantly improved episomal reprogramming efficiency. Elimination of feeder cells and the use of chemically defined media for both the derivation and culture of footprint-free iPSCs bring the reprogramming technology one step closer to clinical applications.

In addition, the feeder cells represent a source of variability. Eliminating feeder cells makes the process more amenable to industrialization. The method was successfully applied and optimized for several cell types including human skin fibroblasts, adipose tissue-derived cells and cord blood cells.

“This publication underscores CDI’s commitment to industrialized human biology,” said Dr. Yu. “This method enables efficient, safe, large scale derivation of iPSCs for research applications and sets the stage for potential clinical use in the future.”

“I wish to congratulate Dr. Yu on her most recent publication. Her work brings us one step closer to the use of iPSC technology in medical treatment,” said Robert Palay, CEO and chairman of CDI.

Chris Parker, Chief Commercial Officer of CDI, added, “Cellular Dynamics is focused on optimizing processes for manufacturing human iPSCs and human differentiated cells for use by the biomedical community. We have demonstrated that we can manufacture human iPSCs and our human iCell® Cardiomyocytes in the quantity, quality and purity required by
our pharmaceutical customers for their drug discovery and toxicity testing programs. We have other cell types, such as hepatocytes, neurons and blood vessel cells in development for these uses as well.”

Parker continued: “iPSCs and the human cells derived from them have potential applicability as therapeutics. However, concerns about exogenous DNA permanently incorporated into the cells have limited development in this area. More recently, several laboratories including our own have developed methods that result in iPSCs that are free of exogenous DNA. Although important advances on the path to iPSC-based therapeutics have occurred, none of the methods developed to date enable efficient production of human cells so that they could be used as safe, efficacious and cost-effective therapeutics. Work done in our laboratory and published in this article demonstrates such a process.”