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Markers of brain cell development may help success of stem cell transplants

07.09.2005

Four sugar-coated faces made by stem cells as they differentiate into brain cells during development have been identified by scientists.

These unique expressions of sugar on the cell surface may one day enable stem cell therapy to repair brain injury or disease by helping stem cells navigate the relative “jungle” of the adult brain, says Dr. Robert K. Yu, director of the Institute of Neuroscience and the Institute for Molecular Medicine and Genetics at the Medical College of Georgia.

“These glycoconjugate markers are like specific addresses that characterize the cell at that particular moment. We call them stage-specific embryonic antigens,” says Dr. Yu of recognition molecules that assist in the unbelievably rapid assemblage of 100 billion to 200 billion cells into a brain in nine months.

The four compounds – two glycolipids, GD3 and O-acetylated GD3, and two glycoproteins, Stage-specific Embryonic Antigen-1 and Human Natural Killer Cell Antigen 1 – were known, but their role in helping cells migrate where and when needed was unknown.

The findings of Dr. Yu, Postdoctoral Fellow Makoto Yanagisawa and Dr. Sean Liour, co-director of MCG’s Human Stem Cell Bank, are being presented during the biannual International Symposium on Glycoconjugates, Sept. 4-9 in Florence, Italy. Dr. Yu is a meeting organizer and is chairing the session on Regulatory Mechanisms for Glycolipid Expression and Intracellular Trafficking.

“We are all sugar-coated, really,” says Dr. Yu, who studies these cell surface molecules that change constantly during development. “There is an abundance of sugar on the cell surface, not only that defines the cell’s properties but also help cells recognize each other and stick together,” he says, noting how like cells bind to form an organ.

During brain formation, for example, cells are constantly changing their sugar face and their function to meet the immediate biological needs. They travel a sort of neuron interstate laid out by the first stem cells formed in development before rapid cell migration and transformation begins. “These ‘interstates’ are called Bergmann glia or glial fibers. They serve as guidance for the neuronal cells to migrate,” Dr. Yu says of the network that is maintained in the adult brain despite the fact that mature neurons don’t really change.

Conditions such as trauma, spinal cord injury and stroke can destroy these travel networks as well as brain cells. Labs such as Dr. Yu’s are doing stem cell transplants to re-establish roadways and get undifferentiated stem cells to repopulate such ravaged areas. He hopes the new developmental markers will help in this effort by showing what cell surface molecules should look like – and consequently how the cells should act – at certain points along the way.

Two of the biggest problems facing stem cell transplantation are functional recovery – getting the cells to do the right job once they arrive at a target organ – and controlling their proliferation so they don’t start forming tumors, says Dr. Yu.

MCG Biochemist Erhard Bieberich is exploring the potential of the lipid ceramide, which helps eliminate potentially harmful cells during brain development, to halt unwanted proliferation of transplanted stem cells.

Dr. Yu hopes the new developmental markers will help with the other problem. “There are other players, but these are important factors that help the brain form. I think it’s a good start. Now that we have these to use as examples, discovery of other markers should come faster.”

The work was funded by the National Institutes of Health, the Children’s Medical Research Foundation in Chicago and the Cerebral Ataxia Association in Taiwan.