Twelve weeks later, the 15 paralyzed rats that got human stem cells partially recovered control of their hind limbs. Moreover, their hind limbs were 40 percent stronger than control animals'. By 24 weeks, 11 of the 15 turned over at least three seconds faster when placed on their backs than before getting the human cells. Control rats did not improve, on average, over the 24 weeks of the study.

In paralyzed rats, Kerr and his team found that most of the implanted human cells migrated into the spinal cord, and many became cells of the nervous system -- astrocytes, neurons and even motor neurons -- while in uninjured animals the transplanted cells just sat on the spinal cord's outer surface. However, even in injured animals, only about four human cells per rat became motor neurons that actually extended out of the spinal cord and into muscle, potentially creating a circuit that could control movement.

"We saw some physical recovery, and we saw human stem cells that had become motor neurons, but it turns out that the two observations weren't related," says Kerr. "We saw functional recovery that wasn't due to new neurons, and we had no idea how that could be possible."

Kerr then discovered that the rats' own neurons were healthier in animals that received human stem cells. In subsequent laboratory experiments, Kerr found that the human stem cells produced copious amounts of two key growth signals. These were transforming growth factor-alpha (TGF-alpha), which promotes neurons' survival, and brain derived neurotrophic factor (BDNF), which strengthens their connections to other neurons. When the scientists blocked these two signals in the laboratory, the stem cells' beneficial effects disappeared.

"Even before motor neurons die, connecting neurons peel back as if
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
27-Jun-2003