Boost for brain stem-cell implants
Protein cocktail persuades stem-cell grafts to become neurons.
11 November 2002

Implanted neural stem cells usually don't develop properly.
© Ping Wu

A simple protein shake coaxes human neural stem cells from fetuses to develop into proper neurons when implanted into live animals' brain or spinal cord. The technique jumps an important hurdle on the path to stem-cell therapies.

To fix neurodegenerative diseases and repair spinal-cord injuries, new neurons must grow in the place of the damaged ones. Unfortunately, most engrafted neural stem cells either don't develop, or turn into support cells rather than neurons, even though they have the potential to grow into any type of cell.

"We used proteins involved in the development of neurons to point them in the right direction before they are engrafted," says team member Ping Wu of the University of Texas Medical Branch in Galveston. "So what is happening to the cells is natural for them."

Wu's team exposed neural stem cells from human fetuses to different combinations of growth factors and support proteins. By trial and error, they identified a cocktail of three proteins that directs the cells to become functional neurons in culture dishes1.

In the brains and spinal chords of healthy rats these primed cells develop almost exclusively into neurons, including the cholinergic type that is critical to the spinal cord and brain regions that many neurodegenerative diseases affect. When untreated cells are implanted, very few neurons develop.

It is somewhat of a surprise that this works
Sally Temple
Albany Medical College

"The treatment seems to shift the balance in these cells - they develop into specific types of neurons based upon where they are engrafted," says stem-cell specialist John Gearhart of Johns Hopkins University School of Medicine in Baltimore. "The environment is clearly directing the outcome."

Others are more cautious. "It is somewhat of a surprise that this works and is a bit of a mystery," says neuroscientist Sally Temple of Albany Medical College in New York state. "It will be interesting to see if these cells are making the right connections and to be sure that they don't form tumours in these animals further down the road."

Wu agrees. "We want to find out if the primed cells can differentiate in the same manner in animal models of central-nervous-system disease or injury before we seriously consider using them in humans," she says. Treatments involving fetal cells are the most controversial of the proposed stem-cell therapies.

Michael Stebbins is an editor on Nature Genetics

Wu, P. et al. Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat. Nature Neurocience, 5, 1271 - 1278, (2002). |Article|

© Nature News Service / Macmillan Magazines Ltd 2002

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