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Lab-Made Heart Cells Found Useful for Research, Testing

Joseph Wu (Stanford University)

Joseph Wu (Stanford University)

Researchers at the Stanford University School of Medicine in California have devised a process for generating artifical heart cells from the skin of patients with a common cardiac condition. Their findings appear today in the journal Science Translational Medicine (paid subscription required).

The team led by Joseph Wu, a professor of cardiovascular medicine and of radiology at Stanford (pictured right), with postdoctoral fellow and first author Ning Sung created cells resembling heart cells from the skin of patients with dilated cardiomyopathy, a leading causes of heart failure and heart transplantation in the U.S. Their process uses induced pluripotent stem cells, a technology employed to create lab-generated stem cells from patients with Parkinson’s disease and amyotrophic lateral sclerosis (ALS), among others.

Dilated cardiomyopathy is a condition in which the heart becomes weakened and enlarged, and it cannot pump blood efficiently. The decreased heart function can affect the lungs, liver, and other organs. Many cases of dilated cardiomyopathy can occur sporadically and without an apparent cause, but it can also be inherited through genetic mutations.

The Stanford team took skin cells from biopsies in seven members of a family with inherited dilated cardiomyopathy, and reprogrammed the skin cells to make induced pluripotent stem cells. The authors then used cocktails of specific growth factor molecules to coach the stem cells into becoming beating cardiac cells.

The lab-generated cells may have had heart beats, but they exhibited properties and behaviors more like diseased rather than healthy heart cells. The new cells carried the genetic TNNT2 mutation associated with dilated cardiomyopathy. The cells also had an altered calcium cycle needed for heart cell contraction, as well as weakness and more sensitivity to stress than normal heart cells.

The Stanford researchers treated the diseased cells with metoprolol, a beta blocker commonly used to treat cardiomyopathy, and found it decreased the frequency of contractions as expected. The drug also increased the responsiveness of the cells to calcium and, over time, helped resolve some of the structural differences between affected and unaffected cells.

The researchers showed as well that adding a protein called Serca2a, which may inhibit the deleterious effect of the mutated TNNT2 gene, significantly improved the contraction force of the diseased cells. Serca2a is currently in clinical trials as a potential gene therapy for dilated cardiomyopathy.

A reliable source of diseased and normal human heart cells on which to test drugs’ effects prior to clinical use, Wu notes, could improve drug screening, save billions of dollars and improve the lives of countless patients. One of the major reasons cardiac drugs are pulled from the market is unexpected cardiac toxicity, where the drugs damage the hearts they are meant to help. Currently, such drugs are pre-screened for toxic effects on common laboratory cell lines derived from either hamster ovaries or human embryonic kidney cells.

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