Team Genetically Engineers Brain Cells to Grow in Laboratory
A team led by a Salk Institute researcher has developed a way to genetically engineer brain cells that grow indefinitely in the laboratory, giving scientists the possibility of cultivating colonies of specialized neurons to study in ways never before possible.
“This gives us a tool to investigate interactions between (brain) neurons in isolated and controlled conditions,” said Pamela Mellon, a Salk associate professor who led the research. “In the case of our own work on how the brain controls reproduction, it might offer a way to understand conditions like late puberty, PMS or infertility.”
The technique might also provide a way to grow neurons that produce other critical brain secretions, such a dopamine, which is deficient in victims of Parkinson’s disease.
Mellon and her colleagues reported in Friday’s issue of the journal Neuron that they linked a cancer-causing gene called an oncogene to another gene, called a “promoter,” and inserted the combination into a fertilized mouse egg. The added genes were integrated into every cell in the mice’s bodies.
The oncogene was not able to cause a tumor unless it was “turned on” by the promoter. The promoter would not turn on the oncogene until it itself was exposed to a certain hormone, which is present only in a specific area of the brain, the hypothalamus.
The net result was that the mice developed tumors of the hypothalamus. Mello isolated cancer cells from the tumor and found that they would grow and proliferate in the laboratory. From each cell in the tumor they could grow identical progeny of the cells, called “clones.” Mellon is interested in the molecular basis of the reproductive hormone system, so such clonal groups of hormone-producing cells are ideal for study.
“Some of the real advantages are that you can study the hormone production system without influences of all the other kinds of cells in the brain, and without all the chemicals that are present in the blood of an animal,” Mellon said. This should enable researchers to study some diseases of the brain in tissue culture. Dr. Solomon Snyder, a prominent Johns Hopkins University brain researcher, suggested Friday that this could be a useful way to replace hormone-secreting cells in the brain for treatment of a number of diseases, including Parkinson’s. But he said it would be much more difficult to use it to replace cells involved in thought processes.
“Whether it would work for neurons in the brain (outside the hypothalamus), we of course don’t know because they are different.
“I think cortical neurons are going to be difficult,” Mellon agreed, “but at some point in early development they do divide, and if we can find the gene that turns on just when they’re just turning into that type of cell, I think we can get them,” she said.
Researchers at Hana Biologics in Berkeley have also been growing brain cells in hopes of using them to treat Parkinson’s.
Times science writer Thomas H. Maugh II contributed to this story.
