Gladstone scientists discover new method for regenerating heart muscle by direct reprogramming
Next-generation reprogramming of native cells offers therapeutic advantages
Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) have found a new way to make beating heart cells from the body's own cells that could help regenerate damaged hearts. Over 5 million Americans suffer from heart failure because the heart has virtually no ability to repair itself after a heart attack. Only 2,000 hearts become available for heart transplant annually in the United States, leaving limited therapeutic options for the remaining millions. In research published in the current issue of Cell, scientists in the laboratory of GICD director Deepak Srivastava, MD, directly reprogrammed structural cells called fibroblasts in the heart to become beating heart cells called cardiomyocytes. In doing so, they also found the first evidence that unrelated adult cells can be reprogrammed from one cell type to another without having to go all the way back to a stem cell state.
The researchers, led by Masaki Ieda, MD, PhD, started off with 14 genetic factors important for formation of the heart and found that together they could reprogram fibroblasts into cardiomyocyte-like cells. Remarkably, a combination of just three of the factors (Gata4, Mef2c, and Tbx5) was enough to efficiently convert fibroblasts into cells that could beat like cardiomyocytes and turned on most of the same genes expressed in cardiomyocytes. When transplanted into mouse hearts 1 day after the three factors were introduced, fibroblasts turned into cardiomyocyte-like cells within the beating heart.
"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 Dr. Ieda.