Parkinson's approach with stem cells a promising first step

December 01, 2006

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.

The team then injected the cells into the brains of rats with Parkinson's-like symptoms, and watched for 10 weeks. While rats with the disorder walked in circles when prompted to move, as if they were chasing their tails, rats transplanted with the new cells recovered normal function and eventually stopped walking in circles. By eight weeks after treatment, the tail-chasing behavior ended completely, and they were walking and running normally.

Yet when the brains of the animals were examined, the team found tumors within the brain grafts. Goldman said the tumors sprang from stem cells that had started on the road to becoming neurons, but then stalled in their development and grew out of control. The team is working on ways to filter out those cells, to reap the benefits while avoiding the side effects of the approach.

"The appearance of tumors was disappointing, but not surprising," said Goldman. "The goals of this experiment were to create a population of cells that had many more dopamine neurons than previous attempts yielded, and to measure whether a group of cells with so many of these neurons would yield real-life benefits in terms of behavior. We accomplished both tasks. The cells improved the disease symptoms dramatically, beyond what we expected.

"In this first attempt of the technology, we did not attempt to try to absolutely purify the cell population that was transplanted - thus the brain tumors. The experiment confirmed that we need to have an absolutely pure cell population, and we are working on ways to do that."
-end-
The work was supported by the National Institute of Neurological Disorders and Stroke, and the Michael J. Fox Foundation. Other authors of the paper, all at Cornell, are Carine Cleren, Shashi Singh, Lichuan Yang, and M. Flint Beal.

University of Rochester Medical Center

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.