Embryonic stem cells, valued by researchers for their ability to become any kind of tissue that a body might need, also produce druglike compounds that can help ailing organs repair themselves, scientists are reporting today.
The new work offers the most definitive evidence yet that the versatile cells, derived from embryos, can help repair organs two ways: by filling in damaged areas -- the primary focus of stem cell research to date -- and also by secreting potent chemicals that can make tissues rejuvenate themselves.
In the new study, mice treated with chemicals derived from stem cells survived an inherited heart deformity that is usually 100 percent fatal. Tests indicated that the chemicals prompted the animals' defective heart muscles to rebuild themselves -- literally refashioning their mutated hearts into healthy pumps that now appear to be working perfectly.
"I think these [stem] cells are more powerful than people had originally imagined," said Robert Benezra, a molecular biologist at Memorial Sloan-Kettering Cancer Center in New York, who led the study with Diego Fraidenraich.
Researchers emphasized that the technique is a long way from being tested in people. For one thing, the ailing mice were dosed with stem cell chemicals before they were born. That gave their mutated hearts a chance to remodel themselves before birth -- an approach unlikely to be tried in humans anytime soon because of technical and ethical concerns.
But scientists speculated that stem cell-derived compounds could help diseases of adulthood, too. Many conditions, including chronic heart disease, involve patterns of abnormal gene activity, scientists said, which the stem cell compounds may be able to correct.
The goal is to harness the chemical signals by which stem cells coordinate the development of fetal organs in the womb, then recapitulate the process in adulthood to resculpt degenerating organs into a more youthful condition.
"Most of the work on stem cells to date has focused on how to get these cells to turn into a heart cell, a kidney cell, a bone cell or whatever it is you need," said Craig Basson, director of cardiovascular research at Cornell University's Weill Medical College in New York, who was involved in the mouse study. "The key scientific finding here is that stem cells can also modify the cells that are already there, to repair, in this case, injured hearts."
Previous experiments had hinted at this potential. In research described last summer in the Journal of Neuroscience, Jeffrey Rothstein, John Gearhart, Douglas Kerr and colleagues at Johns Hopkins University School of Medicine injected a kind of embryonic stem cell into the spinal fluid of rats that had paralyzing motor neuron injuries. Weeks later, the rats that got the cells had largely recovered while those untreated remained paralyzed. Tests indicated their recovery was not a result of the stem cells turning into replacement neurons but was the result mostly of chemicals secreted by the stem cells, which restored the damaged neurons' ability to work.
In the new work, described in today's issue of the journal Science, the New Yorkers injected a few embryonic stem cells from healthy mice into the embryos of mice with a genetic defect that blocks normal heart development. A few of the injected cells did become heart cells, but tests showed it was two substances the cells produced -- gene-regulating compounds known as IGF-1 and WNT5a -- that really saved the mice.
Stem cells were placed not into the embryos themselves but into the bodies of the pregnant mother mice. The cells could not cross the placenta into the developing fetuses, but the compounds the cells secreted did, and those compounds corrected the fetal heart defects.
"It's a first," said Michael F. Clarke, a developmental biologist and professor of internal medicine at the University of Michigan Medical School. He said the work had "huge significance" for showing that stem cells can overcome genetic errors -- not by fixing aberrant genes by "gene therapy," an approach that has failed repeatedly over the years, but by providing embryonic chemicals that can directly control organ development, making the defective gene irrelevant.
He and others said they doubted that stem cells from adults -- which opponents of embryo research favor for research -- can make the same regenerative compounds.
Brigid Hogan, chairwoman of cell biology at Duke University Medical Center, applauded the study but cautioned that it could take many years to identify the many potentially therapeutic compounds secreted by stem cells; purify them or make synthetic versions of them; and find the best way to get them where they are needed in the body.