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Stem Cell Molecules Repair Genetic Damage

They sent signals that fixed damaged heart cells in mice, study says

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HealthDay Reporter

THURSDAY, Oct. 7, 2004 (HealthDayNews) -- Researchers report that embryonic stem cells sent molecular signals that repaired fatal genetic damage to heart cells in laboratory mice.

The study opens the possibility -- admittedly distant -- that the signal-carrying molecules could be used to repair damage in human hearts and other tissues, researchers said.

The study was done with "knockout" animals whose heart cells were genetically engineered to lack a key gene so they would develop a lethal defect before birth, said Robert Benezra. He is a member of the cancer and genetics program at Memorial Sloan-Kettering Cancer Center in New York City, and lead author of a report on the experiment that appears in the Oct. 8 issue of Science.

"We were trying to rescue the knockout animals, to see if we injected stem cells into embryos we could partially repair the damage," Benezra said. "To our surprise, the animals were actually born, and when we looked at their hearts they seemed normal, even though only 10 percent of their heart cells originated from the stem cells."

Stem cells are unspecialized cells that can develop into many different types of specialized cells. Researchers believe these cells may be the key to developing treatment for diseases such as Parkinson's, Alzheimer's, spinal cord injuries, arthritis and many others.

Embryonic stem cells hold the most promise because they are "pluripotent." That means they can develop into many different types of cells. Adult stem cells are considered "multipotent" and aren't believed to be able to transform into as many types of cells as embryonic stem cells.

Research on embryonic stem cells is limited because of President Bush's decision in August 2001 to only allow federal funding for research on stem cells derived from embryos that had already been destroyed. Most researchers depend, at least in part, on federal funding.

The Memorial Sloan-Kettering researchers have identified two molecules that carry the repair signals, Benezra said. They are insulin-like growth factor 1 (IGF-1) and another designated WNT5a. Both have been known to be involved in heart cell growth and cancer, but this is the first report of them having a role in repair of genetic damage, he said.

Benezra said he and his colleagues are trying to identify other such signal-carrying molecules, as part of a far-ranging research effort.

"One thing we would like to know is how general this effect is," he said. "Can other types of genetic disorders be corrected this way? We certainly want to know if other types of tissue defects can be repaired this way."

Benezra declined to discuss his research plans in detail because "we would like to have at least a first jump" in what is rapidly becoming an intensely competitive field.

One competitor, Dr. Andre Terzic, professor of experimental therapeutics at the Mayo Clinic, had only praise for the Memorial Sloan-Kettering work. He said it "elegantly demonstrates that stem cells have the potential to secrete clues that recruit other cells to become what they should become."

The report helps provide an answer to a puzzle in the new field of regenerative medicine, which centers on use of stem cells, Terzic said.

"It is a little puzzling that we often get a relatively low number of cells that are incorporated in the damaged area, and yet get robust repair outcomes," he said. "In addition to replacing damaged cells, stem cells must bring something new with them."

Terzic has coined a name for that something. He calls the signal-carrying molecules "secretones." They are "as important as the stem cells themselves," Terzic said.

Several other signal-carrying secretones have been identified in the Mayo Clinic laboratory, Terzic said. They will be described in a forthcoming scientific paper, he added.

"The proteins themselves might not be new, but where they come from and how they could drive cardiac cell differentiation are of great interest," he said. "Indeed, we are very excited in this particular area."

More information

The National Institutes of Health offers a primer on stem cell research.

SOURCES: Robert Benezra, Ph.D., member, cancer and genetics program, Memorial Sloan-Kettering Cancer Center, New York City; Andre Terzic, M.D., Ph.D., professor, experimental therapeutics, Mayo Clinic, Rochester, Minn.; Oct. 8, 2004, Science

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