Scientists discover new method for regenerating heart muscle by direct reprogramming

Aug 05, 2010

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 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 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 , but it turns out we just needed the right combination of genes at the right dose," said Dr. Ieda.

"The ability to reprogram fibroblasts into cardiomyocytes has many therapeutic implications," explained Dr. Srivastava, senior author on the paper. "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 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 into the heart and all the obstacles that go along with such cell-based therapies." The study results imply that cells in multiple organs within an individual might be directed into necessary cell types to repair defects within the body.

This next generation of direct reprogramming builds on the reprogramming method discovered by Gladstone investigator Shinya Yamanaka, MD, PhD, who found that, by using four genetic factors, adult cells can be reprogrammed to pluripotent cells known as induced pluripotent stem (iPS) cells. Like embryonic stem cells, iPS cells can turn into any of the cell types of the human body.

However, direct cellular reprogramming that does not involve a stem cell state solves some of the safety concerns surrounding the use of stem cells. Going directly from one adult cell type to another would eliminate the risk that some stem cells might develop inappropriately to form tumors.

While direct reprogramming may offer some advantages over Yamanaka's original method, additional work will be necessary to refine the method and bring it closer to a practical therapeutic strategy.

"Direct reprogramming has not yet been done in human cells," Dr. Srivastava explained. "And, the hope is still to find small molecules, rather than genetic factors, that can be used to direct the cell-fate switch."

Explore further: Researchers successfully clone adult human stem cells

More information: Srivastava et al.: “Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors.” Publishing in Cell 142, 375-386, August 6, 2010. DOI:10.1016/j.cell.2010.07.002

Related Stories

Process for expansion and division of heart cells identified

Feb 17, 2009

Researchers at the Gladstone Institute of Cardiovascular Disease (GICD) and the University of California, San Francisco have unraveled a complex signaling process that reveals how different types of cells interact to create ...

Induced pluripotent stem cells repair heart, study shows

Jul 20, 2009

In a proof-of-concept study, Mayo Clinic investigators have demonstrated that induced pluripotent stem (iPS) cells can be used to treat heart disease. iPS cells are stem cells converted from adult cells. In this study, the ...

Scientists identify key factors in heart cell creation

Apr 26, 2009

Scientists at the Gladstone Institute of Cardiovascular Disease have identified for the first time key genetic factors that drive the process of generating new heart cells. The discovery, reported in the current ...

Recommended for you

Researchers successfully clone adult human stem cells

14 hours ago

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

17 hours ago

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

For resetting circadian rhythms, neural cooperation is key

Apr 17, 2014

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

User comments : 3

Adjust slider to filter visible comments by rank

Display comments: newest first

MaxwellsDemon
not rated yet Aug 05, 2010
The thought of this reaching the therapeutic stage within our lifetimes is staggering. In fact, for the first time I feel completely comfortable calling something ‘miraculous.’
weewilly
not rated yet Aug 05, 2010
It is somewhat of a miracle I suppose. Hope it does really work. The problem with today's medicine is that they might cure you with their medicine and kill you with the bill. You're choice I guess.
danlgarmstrong
not rated yet Aug 06, 2010
These therapies should in the end be relatively inexpensive, as they are ways to get your own body to heal itself. I do hope they start getting past the research stage and into clinics soon.

More news stories

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Male monkey filmed caring for dying mate (w/ Video)

(Phys.org) —The incident was captured by Dr Bruna Bezerra and colleagues in the Atlantic Forest in the Northeast of Brazil.  Dr Bezerra is a Research Associate at the University of Bristol and a Professor ...

Researchers develop new model of cellular movement

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

Impact glass stores biodata for millions of years

(Phys.org) —Bits of plant life encapsulated in molten glass by asteroid and comet impacts millions of years ago give geologists information about climate and life forms on the ancient Earth. Scientists ...