Stem cells pump out healing molecules
Birth defects might be prevented by injecting stem-cell protein.
An injection of embryonic stem cells into female mice saved their offspring from a lethal heart problem. The effect suggests that we might one day use certain proteins from stem cells to repair defective fetuses in the womb or even treat adult disease.
Robert Benezra of the Memorial Sloan-Kettering Cancer Center in New York and his colleagues studied mice that lack working copies of three genes, whose babies normally die before birth due to major heart defects.
Before the mothers conceived any offspring, the researchers injected into their stomachs a set of embryonic stem cells extracted from healthy mouse embryos. When the females later conceived, some of their offspring survived for two days after birth and their heart problem was drastically reduced the team reports in Science1.
The cells must have pumped some kind of heart-repairing substance into the mother's bloodstream, which travelled across the placenta into the babies and directed their heart cells to grow normally. "This is a very surprising result," comments Kenneth Chien, who studies heart disease at the University of California, San Diego.
Benezra and his team went on to show that the healing substance is a protein called insulin-like growth factor 1 (IGF-1). They also identified a second repairing molecule made by the embryonic stem cells, called WNT5a. This molecule does not travel as far in the body as IGF-1, and the researchers don't know whether it reached the embryos in their experiment.
The team showed that both of these molecules together have the potential to entirely reverse the growing animal's heart problem. They injected just 15 healthy embryonic stem cells, which were making both IGF-1 and WNT5a, into mutant embryos. The babies that developed from the embryos were close to normal.
Healing throughout the body
The study opens up a new way of thinking about how embryonic stem cells might be used to treat human disease. "It's an exciting piece of work," says Andre Terzic who studies stem cells in heart repair at the Mayo Clinic in Rochester, Minnesota.
Until now, most biologists have hoped to grow embryonic stem cells into new heart, nerve or muscle tissue and transplant it into the body. But it is not clear exactly how to coax stem cells into forming specific tissues, and there are fears that stem cells transplanted into people might start to divide wildly into tumours.
The study is one of the first to prove that stem cells manufacture proteins that can travel through the body and heal defective cells elsewhere. This implies that doctors could simply inject these proteins, or otherwise mimic their effects with drugs, and would not need to inject stem cells at all.
But the study is a long way from being translated into human therapies. Researchers next plan to test whether these proteins, or others made by embryonic stem cells, can cure a range of other birth defects in the heart, brain or other organs.
If they can, this raises the possibility that some defects in human fetuses might be prevented or treated, if they can be diagnosed at an early stage. For example, mothers might boost their levels of IGF-1 by changing their diet or taking a drug, much as pregnant mothers today can lower the risk of their baby having a spinal-cord defect by taking supplements of folic acid.
It is also possible that IGF-1 or other proteins made by embryonic stem cells might be given to patients after heart attacks, to help repair scarred heart tissue. But any dream about treating patients "is extraordinarily speculative at this point," says team member Craig Basson, a heart biology expert at Weill Medical College of Cornell University, New York.
- Fraidenraich D., et al. Science, 306. 247 - 252 (2004).