A Three-Dimensional Heart Tissue from Stem Cells Improves Drug Testing

Specialists at the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR have designed a three-dimensional heart tissue from human stem cells to test the efficacy and safety of new medications on the heart. Professor Jackie Y Ying, Executive Director at IBN said, “Cardiotoxicity, which can prompt heart failure and even death, is a major cause of drug withdrawal from the market.

Antibiotics, anticancer and anti-diabetic medications can have unanticipated side effects for the heart. So it is vital to test as right on time as possible whether a recently developed drug is safe for human use. But, cardiotoxicity is hard to predict in the early stages of drug development.”

A major part of the problem is the use of animals or animal-derived cells in preclinical cardiotoxicity examines because of the limited availability of human heart muscle cells. Substantial genetic and cardiovascular differences exist between animals and humans.

While moving from animal studies to human clinical trials, there have been a large number of cases whereby the tests failed to detect cardiovascular toxicity. More than 20% of drug attrition has been attributed to cardiovascular toxicity. Existing screening techniques based on 2D heart structure can’t accurately predict drug toxicity, while the currently available 3D structures for screening are difficult to fabricate in the amounts required for the commercial application.

To solve this problem, from human prompted pluripotent stem cells the IBN look into group fabricated their 3D heart tissue from cellular self-assembly of heart muscle cells developed.

They additionally developed a fluorescence labeling technology to monitor changes in beating rate using a real-time video recording system. The new heart tissue presented more cardiovascular specific genes, higher beating rate, and stronger contraction compared with cells in a 2D structure.

Lead researcher Dr. Andrew Wan, who is Team Leader and Principal Research Scientist at IBN said, “Using the 3D heart tissue, we could able to correctly predict cardiotoxic effects in view of changes in the beating rate, even when these were not detected by conventional tests. The technique is simple and suitable for large-scale assessment of drug side effects.

It could also be used to design personalized treatment utilizing a patient’s own particular cells”. On their human heart tissue model the scientists have documented a patent, and want to work with clinicians and pharmaceutical organizations to bring this technology to market.

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