Stem cells to Brain Cells: Study in Rodents Shows Transformation is Possible

Dr. Ronald McKay

A team of researchers led by Dr. Ronald McKay at the National Institute of Neurological Disorders and Stroke (NINDS), have succeeded in converting stem cells in rodents into the specific type of brain cell that is lost in Parkinson's disease. The embryonic stem cells, taken from mice and injected into the brains of dopamine-deficient rats, functioned to produce the neurotransmitter dopamine.

The study is one of the first to show that embryonic stem cells can develop into dopamine-producing neurons that function in the brain, according to Dr. McKay. A report on the study appeared in the science journal Nature in June.

"Dr. McKay's experiments further our understanding of the potential of stem cells to develop into differentiated neurons," said Audrey S. Penn, M.D., Acting Director of NINDS. "They provide proof of the 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 (PD)."

The researchers added a gene called Nurr1 to cultured mouse embryonic stem cells and exposed them to a series of growth factors that caused them to develop into neurons. Nurr1 helps neural precursor cells to change into neurons that produce the neurotransmitter dopamine. The loss of dopamine-producing neurons is a central feature of PD.

To see if the stem-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 brain. These rats demonstrated parkinsonian symptoms on one side of their body.

The researchers found that the grafted cells established functional connections with surrounding brain cells and began to release dopamine.

The research by Dr. McKay's team was conducted with the appropriate use of controls, such as a group of rats that received transplants of embryonic stem cells without the Nurr1 gene, and a third group of rats that received sham operations. Only the rats that received the Nurr1-positive cells showed significant improvement in symptoms.

(See the story on the establishment of a new stem-cell research center at Columbia University.)