Clinical Social Workers: Lightening the Patient's Burden
Improving Patients' Quality of Life Through Pain Relief
Making New Neurons With Stem Cells
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Making New Neurons With Stem Cells
Stem cells hold enormous promise to halt and even reverse the debilitating effects of neurological disorders such as Alzheimer's and Parkinson's diseases. Because stem cells generate nearly every type of cell in the body, scientists hope to use them to replace damaged nerve cells, which cannot regenerate. But among the obstacles researchers have encountered is that the immune systems of animals into which stem cells have been grafted respond to the new cells as invaders and reject them.
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Eleni A. Markakis '87 |
In seeking a solution to this conundrum, neuroscientist Eleni A. Markakis '87 focuses on a subset of stem cells known as neural stem cells, which are harvested from adult brain tissue or embryos, and reintroduced to the brain. Using a patient's own nervous tissue, she hopes, will eliminate the need to suppress the immune system, a practice that leaves patients vulnerable to life-threatening illness. It also allows for far more robust cell survival than using foreign cells.
"We're trying to make new neurons for brains that are diseased or damaged," explains Markakis, an assistant professor of psychiatry at Yale University. "A particular focus in my lab is Parkinson's disease, but I can see the application of cell replacement for everything from spinal-cord injury and multiple sclerosis to possibly, one day, treating Alzheimer's disease."
Identification and Extraction
First, though, neural stem cells have to be found. They can be harvested from adult neural tissue, or teased out of human embryonic stem (hES) cell cultures. The heterogeneity of hES cells—their ability to grow into every type of cell—makes them hugely valuable but also quite difficult to study, since liver and brain cells are lumped together in the same culture dish. Markakis is attempting to alleviate that difficulty by isolating neural stem cells from hES cell lines, making it easier for other scientists to study their potential uses.
In addition, Markakis's laboratory has been isolating neural stem cells from the brain's olfactory bulbs, a promising source for two reasons. First, the tissue in that region is quite prolific; a small sample yields a large number of cells. Second, because the brain contains two olfactory bulbs, victims of traumatic brain or spinal-cord injuries and sufferers of degenerative diseases would not need to sacrifice their sense of smell to reap the benefits of harvesting their own cells to repair damage in their brains.
Plugging In
While her work has the potential to be applied to a range of disorders, Markakis currently is focusing on Parkinson's disease. That illness is primarily a movement disorder resulting from the death of cells in the substantia nigra, giving Markakis a specific spot in the brain to deliver new cells, though getting them to graft successfully remains a very difficult proposition because of the complexity of neuronal circuitry.
"What we're doing is trying to isolate neural stem cells that we can put in that area of the brain, and then trying to connect them to the cells already there, which is just a hot mess," she says. "It's very complicated getting cells to plug in correctly."
Part of the complication is due to the fact that researchers are still trying to determine how different species will respond to grafts of stem cells. Markakis's lab has isolated adult neural stem cells from several species, and her previous work with rats, for example, found that adult-derived stem cells failed to generate neurons when placed back into most brain regions. However, she found quite a different result when she placed primate cells into primate brains. New cells became neurons in every region tested, a surprising result for Markakis since her primary focus has been identification and extraction—not grafting—of neural stem cells.
Promising Results
Indeed, given the number of laboratories around the world working on stem cells and attempting to graft them successfully into the nervous system, Markakis never expected to achieve such results. In fact, she initially launched the experiment to see how many grafted stem cells would die off; that they would thrive barely occurred to her. She and her team will publish the work soon.
"I thought, 'I don't know if this is really going to work.' I had zero expectations," she recalls. "It turns out it really might work quite well. The utility of these cells is far, far greater than has been described. It might all work out better than we think."
Markakis holds a bachelor's degree in philosophy from Bryn Mawr, and the bookshelf in her office includes the complete works of Sophocles mixed in among the various scientific texts. She is clear about her role in the biomedical process, emphasizing that while her lab is not the one that will cure Parkinson's, she wants a more direct role in the effort than those conducting the basic cellular science on which her work is based.
"There are really special people who can do that, and I'm able to use what they are able to produce," Markakis says. "For me, I want to take an animal that's not living properly because it has a chemical form of Parkinson's disease and I want to make it better. Then a physician can apply what we've learned and make a patient better. That's the payoff for me."
Tom Durso writes about science, health care, and business for a variety of publications, including the Philadelphia Business Journal and Family Business magazine.