Weill scientists find new source of stem cells in adult brains

By Kristine Kelly

NEW YORK, N.Y. -- In the March issue of Nature Medicine, researchers at Weill Medical College of Cornell University report the discovery of a new source of neural stem cells in the adult human brain. Dr. Steve Goldman and his group made the startling discovery that glial progenitor cells of the white matter, a common population of support cells first isolated by this group three years ago, are capable of giving rise to neurons as well as to glial cells. The cells also can be grown and expanded in culture, where they continue to produce new neurons and glia together. The cells may therefore be considered multipotential progenitor cells, a form of brain stem cell. Strikingly, these cells may comprise as much as 3 percent of the cells in the adult human brain's white matter, making them incredibly abundant.

Goldman, the Nathan Cummings Professor of Neurology at Weill Cornell, and his colleague Dr. Neeta Singh Roy had first isolated what was initially thought to be a distinct glial progenitor cell from the adult white matter three years ago. But they had noticed occasional neurons in cultures of glial progenitor cells, which led them to ask whether these cells might actually be multipotential stem cells, rather than committed glial progenitors. Their experiments, done with Marta Nunes, a visiting graduate student from the University of Lisbon, revealed that the glial progenitor cells of the human white matter were actually brain stem cells. In other words, the cells were able to divide continuously, while giving rise to many different types of neurons, as well as to the major glial cell types, oligodendrocytes and astrocytes.

Goldman's group also established that the white matter progenitor cells did not need to be specifically reprogrammed in any way to produce neurons. Rather, the cells were capable of producing neurons directly after their isolation, without the need of any manipulation. In fact, when the scientists introduced adult human glial progenitor cells into the brain of a developing rat, they found that the cells developed into different types of neurons and glia, depending on when and where they were introduced.

There are some caveats, though, that serve to distinguish adult neural stem cells from fetal stem cells. The adult cells have a limited and finite capacity for renewal, unlike their fetal counterparts, which are capable of renewing themselves much longer. Also, it is not certain that all of the white matter glial progenitor cells can act as stem cells. The true stem cells may be a select few among the overall population of glial progenitor cells.

Nonetheless, Goldman reports: "These considerations aside, progenitor cells that are multipotential and capable of forming neurons are abundant in the white matter of the adult human brain. These cells may prove to have an important role in the induction and implantation strategies of new cell-based neurological therapies."

In fact, the therapeutic uses of these cells may be profound. The findings of this study may prove essential in developing new cell-based therapies for neurological diseases where neurons are lost, such as in Alzheimer's, Parkinson's and Huntington's, or where neurons are damaged, as in stroke, epilepsy and traumatic brain injury. In addition, understanding the environmental regulation of these white matter progenitor cells could enable researchers to activate the endogenous progenitor cells to restore destroyed populations, removing the need for transplants. On the other hand, it seems likely that many types of brain cancer may arise from these glial progenitor cells, should they go awry. Understanding how to control the proliferation of these cells might then lead to new cancer treatments.

Goldman also is a senior attending neurologist at NewYork-Presbyterian Hospital. Nunes is the first author of the paper and is a graduate student in Goldman's lab, as is contributing author H. Michael Keyoung. Roy is an assistant professor of neuroscience at Weill Cornell. Drs. Robert Goodman and Guy McKhann, the collaborating neurosurgeons on this study, are from the Department of Neurosurgery at the Columbia-Presbyterian Medical Center of NewYork-Presbyterian Hospital. Dr. Maiken Nedergaard, Goldman's long-standing collaborator from the Department of Anatomy and Cell Biology at the New York Medical College, also contributed to the paper with members of her group, Drs. Jian Kang and Li Jiang.

The group's research was supported by the National Institute of Neurological Disorders and Stroke (NINDS), the National Multiple Sclerosis Society, the Christopher Reeve Paralysis Foundation, the American Heart Association and Project ALS.