"Our first hypothesis was that functional recovery came from human cells reconstituting the nerve circuits destroyed by the paralysis-inducing virus we gave the rats," says first author Douglas Kerr, M.D., Ph.D., assistant professor of neurology at the Johns Hopkins School of Medicine. "Some of the tens of thousands of implanted primitive human stem cells did become nerve cells or the like, but not enough to account for the physical improvements.
"Instead, these human embryonic germ cells create an environment that protects and helps existing rat neurons -- teetering on the brink of death -- to survive," he says.
It turns out that the implanted human cells spew out two important molecules that help protect rats' existing nerve circuits. One of the molecules helps promote nerve cells' survival, and the other encourages nerve cells to stay connected to their neighbors, says Kerr.
"The rats that got human stem cells were still far from normal, but even the improvements we saw could be important clinically," says Kerr, who emphasizes that any clinical application is still many years away.
In their experiments, spearheaded and majorly funded by the private organization Project ALS, the scientists first infected rats with a virus (Sindbis) they developed that selectively destroys nerve cells that control muscles in the hind limbs. Lou Gehrig's disease, also known as ALS or amyotrophic lateral sclerosis, is similarly marked by a gradual loss of the nerves that control muscles, although its cause is unknown.
One-third of the animals then received transplants of human embryonic germ cells, which are capable of becomi
Contact: Joanna Downer
Johns Hopkins Medical Institutions