Stem cell research is steadily moving forward. As the award this month of the Nobel Prize in Medicine to Dr. Shinya Yamanaka, who created the first induced pluripotent stem cells (iPSCs), shows, the ability to create stem cells from somatic cells has changed scientific research. Contributing to the research’s advancement has been rapid progress in improving stem cell research products. Examples include the development of non-viral reprogramming systems and animal component–free media. Many of these advances have been facilitated by partnerships between major life science tool providers and specialized stem cell research companies. Many notable iPSC agreements and products involving major life science product companies have been announced this year (see table, page 4). The activity suggests that the use and development of iPSCs research tools is progressing, as scientists seek more efficient, reliable and easier methods for such research.

Cellular Dynamics International (CDI) provides human-derived iPSCs and services. Since the company introduced its first products, iCell cardiomyocytes for toxicity screening, in 2009, it has released iCell endothelial cells and iCell neurons. In June, the company signed an agreement with Life Technologies, which will manufacture and sell the company’s feeder-free Essential 8 Medium, human protein–based Vitronectin substrate for cell growth and the non-viral, non-integrating Episomal iPSC reprogramming vectors. Prior to the agreement, the products had not been commercially available. “The nature of our business is that Life Technologies, and a lot of companies, are a much better manufacturer of media than we could ever be,” explained Chris Parker, chief commercial officer at CDI. In addition, the agreement gives CDI a GMP supplier of media. As Mr. Parker told IBO, “What it allowed us to do was make sure the components can be sourced in a GMP manner—that they can be locked down for a period of time, such that: a) from a manufacturing standpoint, we don’t have to worry about the media changing over time, and b) it’s made in a GMP environment, so the same media could be used not only for research tools but also for any cell therapies moving forward.”

The agreement also enables a standard workflow for scaling up of iPSC lines. “The strategy behind that relationship is that many customers are bringing iPSC lines that they have derived themselves to us to manufacture cells from. The more we can get the field to standardize on components that we already use, [it] will allow us to execute on those relationships much more quickly.”
The adoption of stem cells for use in research has grown due in part to iPSCs, which ended many of the ethical and political challenges created by using human embryonic stem cells (ESCs), according to Mr. Parker. Also, the greater availability of iPSCs has made a difference. “The fact that companies like us exist and are shipping these materials opens up the community,” he said. “Now, we have a whole other population of customers and users that are not necessarily trying to make cells, but they are trying to figure out how to use cells that have been derived from stem cells,” he explained. “If you give scientists access to a new model system, they’re going to come up with creative and interesting and useful ways to leverage that biology.”

Drug research applications for iPSCs include toxicity testing, disease modeling and drug screening. “Our entry point with pharma generally was—because cardiomyocytes were our first product—really toxicity testing because there was this unmet need for having a good cardiac model to understand cardiotoxicity. . . . Now that we can make iPS cells from different individuals, it has moved into disease modeling,” said Mr. Parker. An example of such research is the study of hypertrophy for drug discovery using the company’s iCell cardiomyocytes. The availability of iCell neuron cells has also opened new avenues for drug research, as he explained, as such research was not possible before. “It’s completely uncharted waters. Many pharmaceutical companies were getting out of central nervous system research all together because the models that they had—you couldn’t even introduce the disease model into cell lines or animals because it didn’t represent the biology, so no discoveries were being made,” he noted.

In June, the company launched MyCell Services for iPSC reprogramming, genetic engineering and differentiation into iCell terminal tissue cells. “What the MyCell Services has really done is to say ‘hey, we’ve demonstrated we can make these cells from iPS cells,’ now it’s up to the customer. Pick your genotype. What disease do you want to study? Get us a blood sample, we’ll make their iPS cells, and we’ll make the terminal cells and ship them back to you in a cryovial,” explained Mr. Parker. “It’s no coincidence that our current products represent the three germ layers—endoderm, ectoderm and mesoderm—so we’ve demonstrated that we can differentiate cells in all three of those lineages,” he noted. “Once you have that, then the next step is to do what we call scale out . . . [which is] to be able to manufacture in parallel from multiple iPSC lines’ starting materials, which is unique.”

Another company that signed an iPSC-related distribution agreement this summer is publicly held German firm Axiogenesis. In July, Sigma-Aldrich agreed to market the company’s mouse iPSC–derived cardiomyocytes and smooth muscle cell products, which are sold as cells, application-specific kits and custom services. Axiogenesis offers mouse and human iPSC–derived cardiomyocytes, as well as mouse ESC–derived ESC cardiomyocytes, mouse endothelial cells and mouse smooth muscle cells. Until July, Lonza had distributed the company’s Cor.At mouse ESC cardiomyocytes and services.

Asked about the recent growth in stem cell–related research products and partnerships, Felix Haniel, director of Business Development at Axiogenesis, told IBO that there are several reasons for the growth, including the relative ease now of obtaining pure standardized stem cells for research. “The short answer: good quality human cells (what the market has been waiting for) only recently have become available.” Also, he noted greater acceptance by pharmaceutical companies, following an initial evaluation period for the technology. In addition, he said, “Now prices have come down, and alternative cells with relevant and usable protocols have become available.” Like Mr. Parker, he also noted iPSCs and their use as an alternative to human ESCs have lessened the controversy surrounding stem cell research in general.

Intellectual property (IP) concerns were also an issue. “Now, with the granting of Yamanaka’s patents and the generally accepted view that there will not be a patent battle between Yamanaka, [James] Thompson [who founded CDI] and others, companies can dare to spend money in implementing the technology,” explained Mr. Haniel. Finally, the availability of stem cell–derived cardiomyocytes from multiple commercial sources is important. “Large pharma likes to have a substitute in case the product disappears from the market: now, three suppliers of stem cell–derived cardiomyocytes has started providing cells (Geron, CDI and Axiogenesis), providing security of availability.”

Axiogenesis also offers electrophysiology, toxicology and drug development services based on its stem cell technology. As Mr. Haniel explained, stem cells are used for drug screening when insufficient quantities of standardized and stable primary cells are available. He described Axiogenesis’s in vitro disease model for hypertrophic cardiomyopathy drug development, which utilizes mouse iPSC–derived cardiomyocytes for what he called robust, cheap and quick high-throughput screening. “For instance, you would first induce a disease phenotype in the cell and then screen substances that can revert that phenotype,” he told IBO, describing the process. “This way, you can screen with high throughput a set of substances for the desired effect, even without specifying a theory and a target for a mechanism of action,” he noted. “In the same experiment, you also identify novel targets that work.” Human cells can then be used to validate the results.

To compare cardiac reactions among different groups, Axiogenesis is currently developing cardiomyocytes of major ethnicities. Other new products focus on disease models. “In addition, we already have started producing iPS cells from populations with the genetic predisposition to develop a disease to serve as a disease model at a later stage,” added Mr. Haniel.