Proteins Fuse Adult Stem Cells to Cardiac Muscle

CancerWise - May 2007

   
Cardiologists use adult stem cells in clinical trials to repair hearts after heart attacks, but no one has understood the process – until now.

Significance of results

In the March 16 issue of the journal Circulation Research, researchers describe how the stem cells fuse with heart muscle to create new cells that repopulate the ailing organ.

There are not enough natural stem cells in the body to repair cells after a heart attack, says the study's lead author Edward Yeh, M.D., professor and chair of
M. D. Anderson's Department of Cardiology.

"It is marvelous that adult stem cells can help heal a heart, and by understanding the mechanisms involved, we may be able to refine and optimize the process," Yeh says.

Primary results

Investigators found that the fusion of stem cells to heart muscle is only possible if two proteins are available that stick to each other like Velcro.

Secondary results

The investigators also discovered that these new cells, once fused, divide again in an attempt to produce enough cells to help the heart contract.

"The accepted dogma is that heart cells cannot divide, but we show that fusing stem cells onto muscle cells bestows these cells with a new and wonderful ability to divide again to repair the heart," Yeh says.

Research methods

In laboratory experiments, researchers:

• Added human stem cells to mouse cardiac muscle cells
• Simulated an ongoing heart attack by decreasing oxygen

After placing the stem cells with the cardiac cells, some of the cells spontaneously fused together, but simulating a heart attack led to greater fusion.

During a heart attack, the oxygen supply is markedly reduced, and two molecules known as interleukin-6 (IL-6) and tumor necrosis factor a (TNFa) are released from immune cells.

Researchers then simultaneously exposed the cells to low oxygen, IL-6 and TNFa, and cell fusion increased tenfold. They further discovered that two sticky proteins were induced, and blocking these sticky proteins with antibodies would reduce cell fusion.

The researchers followed up by testing their findings in mice, but fusion was markedly reduced in mice by blocking the sticky proteins, Yeh says.

Background

The study is the latest in a research program conducted by researchers at
M. D. Anderson, the Texas Heart Institute at St. Luke’s Episcopal Hospital and The University of Texas Health Science Center at Houston to investigate stem cell repair of heart and vascular tissue. M. D. Anderson researchers hope to better understand and treat cardiotoxicity related to cancer treatment.

In 2003, the researchers demonstrated that adult stem cells in blood can repair hearts, and that it’s not necessary to take stem cells from bone marrow.

In 2004, they found stem cells use different methods to morph into the two cell types needed to restore heart function.

In animal studies, they showed that human stem cells fuse onto cardiac cells to produce new heart muscle cells. But to form new blood vessel cells, the stem cells mature by themselves to provide cells that patch vessel damage.

What's next?

Because researchers also have discovered that stem cells build new cells to line blood vessels, Yeh says in the future it may be possible to augment rebuilding of heart muscle or restoration of blood vessels.

— From staff reports

Resources:

• Heart Health and Cancer (M. D. Anderson)
• Department of Cardiology (M. D. Anderson)