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Embryonic Mouse Stem Cells Reduce Symptoms In Model For Parkinson's Disease

Date:
June 21, 2002
Source:
NIH/National Institute Of Neurological Disorders And Stroke
Summary:
Embryonic mouse stem cells transformed into neurons in a lab dish and then transplanted into a rat model for Parkinson's disease (PD) form functional connections and reduce disease symptoms, a new study shows. The finding suggests that embryonic stem (ES) cells may ultimately be useful for treating PD and other brain diseases.

Embryonic mouse stem cells transformed into neurons in a lab dish and then transplanted into a rat model for Parkinson's disease (PD) form functional connections and reduce disease symptoms, a new study shows. The finding suggests that embryonic stem (ES) cells may ultimately be useful for treating PD and other brain diseases.

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The study is one of the first to show that ES cells can develop into neurons that function in the brain, according to senior author Ronald McKay, Ph.D., of the National Institute of Neurological Disorders and Stroke (NINDS). The report appears in the June 23, 2002, advance online publication of Nature.* A second study in Nature,** led by Catherine Verfaillie, M.D., at the University of Minnesota in Minneapolis, shows that bone marrow-derived cells called mesenchymal stem cells have many of the characteristics of ES cells.

Dr. McKay and his colleagues added a gene called Nurr1 to cultured mouse ES cells and exposed them to a series of growth factors that caused them to develop into neurons. Nurr1 helps neural precursor cells differentiate, or change, into neurons that produce the neurotransmitter dopamine. The loss of dopamine-producing neurons is a central feature of PD. To see if the ES cell-derived neurons would survive and function in animals, the researchers transplanted the neurons into rats that were missing the dopamine-producing cells on one side of their brains.

These rats have parkinsonian symptoms on one side of their bodies. A similar group of rats received transplants of ES cells without the Nurr1 gene, and a third group received sham operations.

The researchers found that the grafted cells established functional connections with surrounding brain cells and began to release dopamine. The rats that received the Nurr1-positive cells showed significant improvements in symptoms during several behavioral tests. Rats that received cells without the Nurr1 gene showed some improvement in parkinsonian symptoms, but less than those that received cells with the gene. Since undifferentiated ES cells sometimes multiply out of control and form tumors, the researchers measured the number of cells in the grafts at several time points after the transplants. The number of cells in the grafted areas appeared to stabilize by 4 weeks after the transplants, and none of the rats developed tumors.

"Dr. McKay's experiments further our understanding of the potential of stem cells to develop into differentiated neurons," says Audrey S. Penn, M.D., Acting Director of NINDS. "They provide proof of principle that we can start with embryonic stem cells and end up with dopamine neurons that are useful in a model for Parkinson's disease."

Previous studies have shown that neural precursor cells (which are more limited in their potential than ES cells) can grow into neurons that reduce symptoms when transplanted into an animal model of PD. However, neural precursor cells generate dopamine-producing neurons in culture for only short periods, while ES cells can proliferate extensively and may provide an unlimited source of dopamine neurons, Dr. McKay says.

In this study, Dr. McKay's group used a system that allowed them to manipulate the cells at every point until they are transplanted. "Every step of the way is controlled – we are not just putting cells into the brain," says Dr. McKay. The ability to isolate cells with specific properties for transplantation is an important part of their result, he adds. "We now know that we can start with ES cells and end with dopamine neurons. We do not know if we can make dopamine neurons by starting with any other cell type," he says. "It's as if, leaving New York, you have instructions to drive to Washington that will get you there in four and a half hours. It's possible that if you start in Chicago or Minneapolis you might get to Washington, but if you don't have instructions from that location you don't know how long it will take. We have developed the instructions that get us from ES cells to dopamine neurons."

While the results suggest that ES cell-derived neurons may be useful for treating PD and other neurological diseases, they are still preliminary, Dr. McKay says. Researchers need much more information about how the cells interact with the host brain and about their safety before similar strategies can be tested in humans. He and his colleagues are planning studies to address these questions.

The NINDS is a component of the National Institutes of Health in Bethesda, Maryland, and is the nation's primary supporter of biomedical research on the brain and nervous system.

###

*Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee S-H, Nguyen J, Sanchez-Pernautes R, Bankiewicz K, McKay R. "Dopaminergic midbrain neurons derived from embryonic stem cells function in an animal model of Parkinson's disease." Nature, advance online publication, June 23, 2002, DOI: 10.1038/nature00900.

**Jiang Y, Balkrishna NJ, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. "Pluripotency of mesenchymal stem cells derived from adult bone marrow." Nature, advance online publication, June 23, 2002, DOI: 10.1038/nature00870.


Story Source:

The above story is based on materials provided by NIH/National Institute Of Neurological Disorders And Stroke. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute Of Neurological Disorders And Stroke. "Embryonic Mouse Stem Cells Reduce Symptoms In Model For Parkinson's Disease." ScienceDaily. ScienceDaily, 21 June 2002. <www.sciencedaily.com/releases/2002/06/020621081608.htm>.
NIH/National Institute Of Neurological Disorders And Stroke. (2002, June 21). Embryonic Mouse Stem Cells Reduce Symptoms In Model For Parkinson's Disease. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2002/06/020621081608.htm
NIH/National Institute Of Neurological Disorders And Stroke. "Embryonic Mouse Stem Cells Reduce Symptoms In Model For Parkinson's Disease." ScienceDaily. www.sciencedaily.com/releases/2002/06/020621081608.htm (accessed December 22, 2014).

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