Contacts: Lois Kehl, Research Associate, School of Dentistry, (612) 624-5693, [email protected] George Wilcox, Department of Pharmacology, (612) 625-1474, [email protected] Deane Morrison, News Service, (612) 624-2346, [email protected]
Recorded sound bites from Wilcox are available via the University NewsLine at (612) 624-6065.
Regeneration of functional nerve cells from postnatal rat spinal cord achieved by U of Minnesota researchers
A team of University of Minnesota researchers has regenerated functioning nerve cells from cervical (neck) nerve tissue taken from young rats, whose spinal cords were once thought unable to grow new nerve cells.
The finding builds on work by other researchers that had shown regeneration of nerve cells from the lower spine but did not clearly demonstrate that the new cells were functional. The Minnesota researchers, who will publish their work in Friday's issue of Science, cautioned that while their finding is a necessary step toward eventual treatment for upper spinal cord injuries, a cure must await many more years of work.
"We're excited because this is the first time anyone has demonstrated that nerve cells generated from postnatal mammalian spinal cord can actually function," said Lois Kehl, lead investigator for the study. "That is, they produce electrical impulses known as action potentials, a hallmark of working neurons. It's important to note that while this is not a treatment for spinal cord injury, it is a step toward that goal."
Besides demonstrating that the new nerve cells were functional, the work differs from previous work in the field in two ways. First, other researchers reported difficulty generating new nerve cells from the cervical area, where the most serious injuries occur. Instead, they had the greatest success with spinal tissue from the lower back. Second, Kehl and her colleagues were the first to maintain existing nerve cells in the culture where new ones were generating.
The researchers began their studies by removing cervical nerve tissue from 15- or 16-day-old rats and culturing it on coverslips. Because the tissue contained not only nerve cells but other cells that resemble nerves, they had to identify nerve cells before they could count them. They did this by treating the tissue with antibodies that recognized proteins unique to nerve cells. Counts revealed that hundreds of nerve cells were present in each culture at the beginning, but that the number had increased to tens of thousands after two weeks.
The researchers also treated the cultures with bromodeoxyuridine, a chemical that is incorporated into the DNA of dividing cells. Many nerve cells contained the chemical, showing that those cells had been produced by cell division after the tissue was taken from the rat. The cell division took place not in mature nerves, but in an unknown number of small round precursor cells whose descendants matured into full-fledged nerve cells. The key to regenerating the nerve cells may lie in the culture fluid, the researchers said.
"Scientists think that nerve cells in intact spinal cord may be somehow inhibited from producing new nerve cells," said pharmacology professor George Wilcox, in whose laboratory the work was performed. "We think the culture medium is a permissive environment for nerve growth, but we don't know just what allows it to happen."
The researchers are now working to identify the factors responsible for promoting nerve cell growth in cultures like the ones in Wilcox's lab. It will require the work of many laboratories to find all the factors, said Kehl, who added that future studies will include determining what combination of factors will promote the growth of new nerve cells in whole animals. The current work stemmed from Ph.D. research by Kehl, a dentist, in the area of pain relief.
"I was trying to find a way to culture the spinal nerve cells that are important in pain transmission so that I could study them," said Kehl. "This was a totally unexpected finding." Pharmacology graduate student Carolyn Fairbanks, another author on the paper, underscored the importance of investigating intriguing but unexpected leads in research. "One reason why this project was able to come to fruition is that we three who were students then were allowed to pursue, full-time, an exciting finding outside the main focus of Dr. Wilcox's research," Fairbanks said. Pharmacology graduate student Tinna Laughlin was the third student on the project. The work was supported by the National Institute of Dental Research and the National Institute on Drug Abuse.
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