Cell reprogramming breakthrough could mend broken hearts

Heart disease remains one the biggest killers in the Western world. When a heart attack or heart failure occurs, permanent damage often affects the heart, destroying live cells and leaving the patient with irreversible scarring. This scarring can often lead to a terminal condition or increase the risk of danger of future heart attacks. Now scientists at the Gladstone Institute of Cardiovascular Disease (GICD) have discovered a new technique to create healthy beating heart cells from structural cells. These advancements mean that in the future doctors could be able to repair damaged hearts.

Our human heart comprises of cardiomyocytes (beating heart cells) and cardiac fibroblasts, which provide a support structure and secrete signals. In research published in the current issue of the Journal Cell, scientists were able to successfully reprogram fibroblasts within the heart to transform them into cardiomyocytes.

"Scientists have tried for 20 years to convert nonmuscle cells into heart muscle, but it turns out we just needed the right combination of genes at the right dose," said lead researcher Dr. Masaki Ieda.
With this success of these trials the researchers have discovered evidence which would suggest that independent adult cells within the body can be reprogrammed from one cell type to another whilst by-passing the stem cell state. This discovery could have repercussions in all areas of medicine. Whilst direct cellular reprogramming may erase the issues involving the use of stem cells, it could also remove the risk that some stem cells may later develop into tumors.

The first stage of the cellular reprogramming occurs over three days, before the cells start to adopt the characteristics of cardiac muscle. However it may take up to seven weeks before the cells are fully reprogrammed into healthy beating heart cells.
"The ability to reprogram fibroblasts into cardiomyocytes has many therapeutic implications," said GICD director Dr. Deepak Srivastava. "Half of the cells in the heart are fibroblasts, so the ability to call upon this reservoir of cells already in the organ to become beating heart cells has tremendous promise for cardiac regeneration. Introducing the defined factors, or factors that mimic their effect, directly into the heart to create new heart muscle would avoid the need to inject stem cells into the heart and all the obstacles that go along with such cell-based therapies."

While direct cellular reprogramming hopes to offer many advantages, further laboratory work will need to be carried out before this technique can be used easily and effectively within our hospital systems.
"Direct reprogramming has not yet been done in human cells," Dr. Srivastava added. "And, the hope is still to find small molecules, rather than genetic factors, that can be used to direct the cell-fate switch."

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