Brain cells derived from human embryonic stem cells improved the condition of rats with Parkinson's-like symptoms dramatically, but the treatment caused a significant problem - the appearance of brain tumors - that scientists are now working to solve.
The study is featured on the cover of the November issue of Nature Medicine.
The work was reported by neurologist Steven Goldman, M.D., Ph.D., professor of Neurology at the University of Rochester Medical Center and chief of its Division of Cell and Gene Therapy, and Neeta Roy, Ph.D., assistant professor of Neurology at Cornell's Weill Medical College.
"The results are a real cause for optimism," said Goldman. "These animals with severe Parkinson's symptoms had a dramatically improved outcome after treatment. Now we have a new problem to work on, how to achieve the same benefit without creating tumors. But we expect to be able to solve this problem within the next year or two, using new approaches to cell sorting that we've been developing."
"All in all, this is the way medical discoveries move forward: One step at a time."
Goldman has spent much of his career creating ways to isolate stem cells, discovering the molecular signals that help determine what specific types of cells they become, and then re-creating those signals to direct the cells' development. It's the versatility of stem cells that make them so attractive. If scientists like Goldman are successful directing their development, such cells could provide a ready source of cells custom made to treat a given disease - for instance, myelin-producing cells for multiple sclerosis, or the specific types of cells that die in patients with Parkinson's or Huntington's diseases.
In the experiment reported in Nature Medicine, Goldman, Roy and colleagues set out to grow brain cells called neurons that produce dopamine, a crucial brain chemical lacking in patients with Parkinson's. They began by isolating human embryonic stem cells, then using genes such as "sonic hedgehog" and fibroblast growth factor 8 that make chemicals in the normal brain environment. Such signals are the body's natural way of directing stem cells to develop into the specific cells needed.
Past attempts at using stems cells to make this type of neuron had achieved modest success, but only relatively small numbers could be produced in tissue culture. To improve upon this, Roy and Goldman attempted to re-create the natural environment of the developing brain as much as possible, so it would seem to the stem cells that they were developing in the part of the brain where dopamine neurons are normally made. The team did so by raising the cells together with brain cells known as astrocytes, which had come from the same brain region. These cells have long been known to play a crucial role nourishing neurons.
The result was that more than two-thirds of the stem cells developed into precisely the type of cell needed to treat Parkinson's disease - dopamine-producing neurons. That percentage is far higher than any previous experiment had achieved.