Report:
Nose news for new nerves
Investigator: Hans Keirstead
3 November 2002
by Apoorva Mandavilli
A unique group of human cells, isolated
from the nasal epithelium, can help rats with injured spinal
cords recover their ability to walk, US researchers reported
today. The approach is one of several in the revitalized field
of nerve regeneration.
The prevailing dogma in regeneration holds that "axons grow
where the [growth promoting] cells go," said Hans Keirstead,
assistant professor of anatomy and neurobiology at the University
of California in Irvine. But researchers have not been able to
take advantage of that concept because growth-promoting cells
generally do not migrate, Keirstead explained.
Embryonic stem cells are one exception to that rule; so are
olfactory ensheathing cells (OECs), which enable the sense of
smell. OECs grow rapidly, are non-tumorigenic, and unlike most
cells of the central nervous system, can replace themselves when
injured. When they are transplanted, the cells can also migrate.
"That's a rare, rare trait," Keirstead said.
In the past few years, several teams have investigated the
ability of OECs to promote axon regeneration and generate new
myelin sheaths, primarily with cells derived from canine and
rodent olfactory bulbs. The researchers have met with mixed
results, ranging from excellent recovery to none at all.
When Keirstead purified OECs from human nasal mucosa and
transplanted them into a rat model of severe spinal injury, there
was some regrowth of neurons in the injured spinal cords, even in
areas with scarring, Keirstead reported. The rats also quickly
regained bladder function and regained some of their ability to
walk.
"This is the first time human OECs prepared in this high-purity
manner have been used to investigate their ability to treat the
injured spinal cord," says Keirstead. "Because our study used
human cells, it has direct significance for clinical use."
Using human OECs has many advantages. Extraction of the cells
is an easy five- minute procedure, and subjects experience no
side-effects, apart from temporary hallucinations of smell,
Keirstead said. They can also be used in autologous transplants,
minimizing most of the complications associated with
transplantation.
OECs are only one of several new promising techniques in
regeneration. At the University of Utah, researcher Ray Lund and
his colleagues have transplanted a human pigment epithelial cell
line and improved vision in a rat model of retinal degeneration.
Yale University researchers, led by neurobiologist Stephen
Strittmatter, have developed a synthetic peptide that blocks the
Nogo gene, which inhibits regeneration. The peptide
promotes new nerve fiber growth in the damaged spinal cords of
laboratory rats, allowing them to walk better, Strittmatter said.
Before any of these therapies can be moved to human trials,
however, they must first undergo extensive testing for safety and
efficacy in human disease.
If scientists can take cues from brain development to devise
the right combination of growth promoting cells and neurotrophic
factors, they may be able to promote neuronal regeneration, said
Keirstead. But, he said, "there's still a lot going on in brain
development that we don't understand."