Feb. 18, 2004 It used to be considered dogma that a nerve, once injured, could never be repaired. Now, researchers have learned that some nerves, even nerves in parts of the brain, can regenerate or be replaced. By studying the chemical signals that encourage or impede the repair of nerves, researchers at the University of Washington, the Salk Institute, and other institutions may contribute to eventual treatments for injured spines and diseased retinas, according to a presentation at the annual meeting of the American Association for the Advancement of Science (AAAS).
Much of this research focuses on stem cells, one of several types of general cells that can give rise to specialized cells, like neurons. It was once thought that human stem cells were only found in embryos, and in bone marrow, where they produce blood cells. But stem cells are also being found in adults, including the brain and the eye. For example, stems cells steadily replace dead neurons in the olfactory bulb, which transmits scent signals to the brain, and the hippocampal dentate gyrus, an area that organizes short-term memory.
However, the pace of stem-cell repairs in humans is slow. And in some cases, stem cells can even impede healing. Stem cells in an injured spinal cord can create a sticky scar that blocks nerve regeneration, according to Dr. Philip Horner, an assistant professor in the Department of Neurosurgery in the UW School of Medicine.
"We've found that the axons, the parts of the nerves that transmit signals, try to regenerate after an injury but get caught in the scar. It's like they're stuck in the mud," Horner said. "We're studying ways that this process is regulated to see if it can be manipulated to promote healing. In other words, we're looking at ways to get the axons out of the mud. One way is to make the mud less sticky by manipulating stem cells that participate in scar formation. Another is to stimulate the axons to push through the scar by providing the cut nerves with molecules that induce elongation. We're using molecular signals called growth factors to simulate the growth of cultured nerve cells in the laboratory."
Horner and Dr. Thomas Reh, professor in the UW Department of Biological Structure, will join Dr. Fred Gage from the Salk Institute for a 12:30 p.m. session Feb. 16 on "Neural Stem Cells in Health and Disease" at the AAAS's annual meeting in Seattle. Gage will present an overview of neural stem cells, Horner will discuss stem cells and the repair of the spinal cord, and Reh will focus on stem cells in the eye.
The same types of cells that create scar tissue in the spinal column can create new cells in the retina of the eye, especially in young animals of some species, according to Reh. The retina is a delicate light-sensitive membrane that transmits light signals to the brain. Many eyes diseases that cause blindness, such as glaucoma and as age-related-macular-regeneration, damage the retina.
Salamanders don't get glaucoma because they can readily regenerate retinal cells. The same is true of newts, frogs, and some types of fish. "We're trying to understand the remarkable regenerative powers of these lower vertebrates, and through this understanding, develop strategies to stimulate regeneration in the human retina," Reh said.
While salamanders can regenerate retinal cells through their life, many other species lose this ability as they age. "At some point in each species life cycle, the stem cells in the retina make a transition from a regenerative cell to a cell that will make a scar in response to injury, like the cells that cause scars in the spinal cord," Reh said. "Chickens make the transition a few weeks after hatching in most of their retina, though they retain some limited capacity to regenerate retinal cells throughout life. In rats, it's only a matter of a few days after the cells are generated that they lose their ability to regenerate other retinal cells."
Human retinas seemingly can't repair themselves, yet in recent studies human retinal cells have grown new neurons when cultured in the laboratory. "The hope is that many of the molecular and cellular mechanisms necessary for regeneration, that serve amphibians so well, are still in place in humans," Reh said. "Future studies from the nervous system, as well as other organ systems, should enable us to define the roadblocks in the regenerative process, and develop strategies to go around them."
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