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Biomedicine

Made-to-Order Heart Cells

Stem cell advance will help drug development.

Last month, Madison, WI-based Cellular Dynamics International (CDI) began shipping heart cells derived from a person’s own stem cells. The cells could be useful to researchers studying everything from the toxicity of new or existing drugs to the electrodynamics of both healthy and diseased cardiac cells.

Heartbeats: Spontaneously beating iCell Cardiomyocyte cells.

CDI’s scientists create their heart cells–called iCell Cardiomyocytes–by taking cells from a person’s own blood (or other tissue) and chemically reversing them back to a pluripotent state. This means they are able to grow or can be programmed to grow into any cell in the body.

The science comes from the lab of CDI cofounder and stem-cell pioneer James Thomson of the University of Wisconsin. In 2007, his lab published a study led by postdoc Junying Yu in the journal Science that detailed how to reverse virtually any human cell back to an undifferentiated state known as an induced pluripotent stem cell, or IPS cell. (Japanese physician and geneticist Shinya Yamanaka also created IPS cells from humans and published details in the journal Cell in 2007.)

“One of the biggest advantages of these cells is we can make them in quantity and on demand,” says CDI CEO Robert Palay. “Before, you had to get heart cells from a cadaver, so there was a limited supply.”

Palay and CDI’s chief commercial officer, Chris Kendrick-Parker, discussed the stem-cell-derived cardiac cells at the JP Morgan Healthcare Conference in San Francisco last week. A customer receives all of the different types of heart cells in a vial about the size of the tip of a little finger; some of the 1.5 million to 5 million heart cells in the vial can be induced to pulse when placed in a petri dish.

CDI designed the cardiac cells primarily to aid drug discovery and to help predict the efficacy and toxicity of different drugs. Other tests might include screens to determine if there are differences in how various ethnicities and other genetic subpopulations respond to drugs–such populations can be at higher risk for side effects from drugs, and at a higher risk for the drugs simply not working. Some researchers also plan to see how cells derived from patients with different types of heart disease respond to particular drugs.

“Using these cells to find out which drugs work on an individual’s cells based on their genetics is a very promising new technology,” says geneticist Leroy Hood of the Institute for Systems Biology in Seattle, “though we have yet to see how promising.”

The cells provided by CDI also offer a ready supply for scientists conducting basic research in how cardiac cells function. But they do not come cheap. Palay says they cost about $1,000 for a vial, compared to about $800 for cells from cadavers, though the latter are not as readily available, and they don’t beat in a petri dish, limiting researchers’ ability to study the electrodynamics of heart cells.

IPS-derived cells also have the potential to become a powerful predictive tool when combined with genetic profiling that identifies genetic predispositions to adverse reactions to drugs. Cells derived from people with DNA markers giving them a high risk for side effects from a drug can be tested to determine if the risk is real before they ever take the medication.

“Before CDI, these cells were very difficult to obtain, and we would only get tiny amounts,” says stem cell biologist Sandra Engle, a senior principal scientist at Pfizer. “This doesn’t work for high-throughput testing for drugs.” Researchers use high throughput processes to test up to thousands of different drug compound candidates to see which work and are safe.

The cells also allow researchers to test cells from the same stem-cell stock over time as they develop drugs, which can take years, explains Engle. “We could not do that before.” Researchers also can check drugs on cells from different types of patients to see if there are different reactions, and study why some cells become diseased.

IPS cells are genetically and immunologically compatible with the person who provided the original cells. This means that cardiac and other cells produced from IPS cells won’t be rejected by a person’s immune system, always a possibility with cells that come from donors, animals, or cadavers.

Because of this, IPS-derived cells for the heart and other tissue may one day be a perfect genetic match for effecting repairs to damaged tissue in the heart and elsewhere, though IPS-derived cells cannot yet be used as spare parts. “Therapies using these cells are still a long way to go,” says Palay. “We don’t know yet know how to graft them to grow in human tissue.”

However, personalized drug testing has the potential to become a powerful predictive tool combining genetic profiling with cell-toxicity screening. It could help determine adverse reactions to drugs in genetically high-risk individuals before they ever take a given drug.

“This is a game changer,” says Engle.”It’s going to dramatically change biology and drug development.”

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