Heart beats are just a stem cell away

Chemical turns embryonic stem cells into muscle.

A team of US chemists has discovered a chemical that can turn embryonic stem cells into beating heart muscle cells. ’This type of research may ultimately facilitate development of drugs that can stimulate tissues to regenerate themselves,’ claims Sheng Ding, who was part of the research team.

Embryonic stem cells (ESCs) are essentially cellular blank slates, able to change (differentiate) into any cell type in the body. As such, they are potential wonder treatments for a range of degenerative disorders, such as heart disease and diabetes. However, their great benefits are currently restricted by the fact that it is difficult to control how they differentiate. Current techniques for turning ESCs into heart muscle cells have a success rate of only around 5 per cent.

Scientists suspect that ESCs differentiate into different cell types in response to different chemical signals, but the exact nature of these signals is still mostly unknown. So a team of chemists from the Scripps Research Institute, La Jolla, California, and the Genomics Institute of the Novartis Research Foundation, San Diego, California, decided to design a synthetic chemical that would transform ESCs into heart cells.

The researchers genetically engineered mouse embryonic carcinoma cells, which have many of the properties of ESCs, to possess a gene coding for a hormone that is synthesised in heart muscle cells. They then linked this gene to a luciferase gene, so that the cell would glow if the heart hormone gene was expressed. Using high-throughput screening, the team tested 100 000 compounds on these cells and discovered around 80 compounds that caused the cells to glow.

With further assays, the researchers narrowed these compounds down to just one: a diaminopyrimidine with a 2-hydroxylamino substitution at the C4 position and a p-methoxy aniline substitution at the C2 position, which they called cardiogenol C. Testing this compound on mouse ESCs, the chemists found that more than 90 per cent of the cells showed signs of changing into heart muscle cells.

Colin McGuckin, a reader in stem cell biology at Kingston University, Surrey, UK, says that this research ’does bring us closer to the end goal of defined cell production’. Nevertheless, he warns that further research will be needed to determine whether cardiogenol C has any detrimental effects on other cell types.

Jon Evans