The prospect of using human embryonic stem cells to treat disease appears a small step closer as the result of two new experiments with the cells, which are mired in political controversy because they are derived from human embryos.
In one report released yesterday, researchers showed that the versatile cells can serve as "biological pacemakers," correcting faulty heart rhythms when injected into the failing hearts of pigs.
In another report, scientists demonstrated for the first time that stem cells can become a cell crucial to vision. Many doctors believe that several vision-destroying diseases could be fought by transplanting these cells directly into the eyes.
Human embryonic stem cells, derived from five-day-old embryos, have the biological potential to morph into virtually all of the 200 or so kinds of cells in the body. Researchers are racing to learn how to direct them to develop into specific types of cells that can be transplanted into failing organs. It is an approach that could launch a new era of regenerative medicine -- but only if the cells prove capable of integrating into existing organs and functioning normally there.
Izhak Kehat and Lior Gepstein of the Technion-Israel Institute of Technology in Haifa and their colleagues sought to test that capacity with stem cells that were growing into heart muscle cells.
The team started with masses of stem cells growing in laboratory dishes, from which they isolated those few that were spontaneously developing into heart cells.
They were easy to spot: They were the ones that were pulsing in unison, as heart cells are apt to do.
In one experiment, the scientists isolated small balls of the human cells -- each ball about the size of the head of a pin, or about 1 million cells -- and placed that little mass into a lab dish with rat heart cells.
The cells of each species, rat and human, beat at different rates at first. Within 24 hours of living together, however, the combined masses of cells coordinated their pulsing into a single rhythm.
"At least in the dish, they integrated structurally, mechanically and electrically," Gepstein said.
But could stem-derived heart cells help set the pace of a heart in a live animal?
To find out, the team threaded a probe into the hearts of 13 pigs and made a small burn in the area that regulates the heart beat, causing a permanent severe slowing of those animals' heart rates. The injury mimicked a human heart rhythm disorder that could be caused by disease or a small heart attack.
Then they injected about 100,000 of their human embryo-derived heart cells into the damaged pig hearts. Eleven of the 13 returned to faster heart rates, the team reported in yesterday's advanced online edition of Nature Biotechnology. There was no improvement in control animals that did not receive the cells.
"It's not like tomorrow people are going to be waiting in line for biological pacemakers," Gepstein said. "But we were happy to see after a few days a new rhythm arose," providing what he called "proof of principle."
A second report -- appearing in the fall issue of the journal Cloning and Stem Cells -- describes the first documented growth of retinal pigment epithelial cells, or RPE cells, from human embryonic stem cells.
RPE cells, which are related to nerve cells, live inside the eye and provide essential "housekeeping" duties for the rods and cones -- the light-sensitive cells in the retina. RPE cells scavenge the retinal area for cellular debris, sucking old material up like little vacuum cleaners. And they secrete substances that aid in tissue repair within the eye.
The loss of RPE cells in middle and old age is a major cause of age-related vision loss, including macular degeneration. That disease is the leading cause of blindness in people older than 60, affecting 30 million people worldwide. Doctors have begun to experiment with RPE cell transplants into people's eyes, but the approach has been plagued by problems -- including an inadequate supply of cells.
In experiments led by Irina Klimanskaya and Robert Lanza of Advanced Cell Technology in Worcester, Mass., human embryonic stem cells grown in lab dishes under certain conditions spontaneously became RPE cells, offering a possible solution to the supply problem.
Moreover, the ACT system involves no animal cells or products -- a feature the Food and Drug Administration has said will be important as it considers granting permission to test stem cell-derived cells in people.
Lanza said the company hopes to complete transplant studies in large animals during the next year, after which it will apply for permission to test the cells' safety and therapeutic value in the eyes of people with RPE-related vision loss.
Not all stem cell colonies worked equally well, Lanza noted, touching on a hot area of political debate. Six of the colonies -- those developed by Harvard researcher Douglas Melton with private funds -- "worked like a charm," Lanza said, as did two colonies developed by ACT.
But the three colonies developed by a Wisconsin team -- among the few approved by President Bush for study with federal dollars -- worked only "very reluctantly," Lanza said. Bush has banned federal funding for research on newly derived stem cell lines in order not to encourage the destruction of human embryos, but Lanza said his work shows that policy is short-sighted.
"It's becoming clear that each colony is different and can do different tricks," Lanza said. "To limit federally funded research to just a handful of lines is a mistake."