Genetically engineered cardiomyocytes: hope for the ageing population

Cardiovascular disease is the leading cause of death is Australia, accounting for approximately one-third of deaths in 2006. Consequently, researches have been trying to develop a way to engineer cardiac cells in order to treat cardiovascular diseases. Unlike other cells in the body, cardiac cells are not able to regenerate.

Researches Jun Takeuchi and Benoit Bruneau at the Gladstone Institute of Cardiovascular Disease in San Francisco have found that they can develop mouse embryos with beating cardiomyocytes by adding cardio-specific genes.

Many researchers have attempted to generate heart cells, but none have been able to find the right combination of transcription factors to produce cardiac cells. Some have succeeded in successfully transforming cells using transcription factors. Thomas Graff has had success with blood, Doug Melton with insulin-producing cells and Shinya Yamanaka with induced pluripotent stem cells.

Bruneau’s success comes from adding the gene for a different type of protein. It is a chromatin remodeller call Baf60c (Smarcd3) that Bruneau has previously identified as important in differentiation of cardiac cells. Bacf60c combined with cardiac transcription factors Gata4 and Tbx5, formed cardiomyocytes in the amnion of the embryo. The amnion is comprised in part of mesoderm, it is the same broad category of germ layer to which heart cells belong. However, it grows away from the embryo and does not form part of the body. The researches have not been able to reach the desired location. Bruneau and his research team are now applying the technique to cells derived from adult mice because they will more readily translate into heart therapies. The next step for Bruneau is to work out how the transcription factors induce the cardiac differentiation.

Scientists still have a long way to go before any success is beneficial to humans, but research has made great progress since the discovery that cultured cells were transformed into muscle.

Image - green spots are new heart cells in extra-embryonic tissue that does not normally produce cardiomyocytes

Reference: Monya Baker. (2009) " Recipe for heart cells from amnion". Nature

http://www.nature.com/stemcells/2009/0905/090507/full/stemcells.2009.68.html