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Converting stem cells

August 01. 2003 6:01AM
Diane Chun
Sun Medical Writer
Gainsville Sun

With just the right coddling in the laboratory, can adult stem cells taken from bone marrow be coaxed into becoming brain cells?

That's a question a team of University of Florida researchers hope to answer with a four-year, $1.2 million grant award from the National Heart, Lung and Blood Institute.

Stem cells are primitive master cells that can produce a whole range of cells and tissues.

Transplantation of bone marrow stem cells has become fairly routine. Stem cell transplants now treat blood conditions such as lymphoma, myeloma and some leukemias, aplastic anemia and immune system deficiencies.

Recent research suggests that some adult stem cells can change into different tissues. But scientists are split on whether the cells are just fusing with the target organ - the liver, for example - or actually becoming liver cells.

"We're looking at the ways in cell culture that we can affect the choice of a stem cell to go down particular cell fate lineages, and we're devising conditions and factors that promote turning one type of stem cell into another type of tissue," said Dennis A. Steindler, a professor of neuroscience and neurosurgery at UF's College of Medicine who also is affiliated with UF's McKnight Brain Institute and the UF Shands Cancer Center.

"The stem cell is a very indecisive cell," Steindler said. "It doesn't know what it will turn into, it's undifferentiated. The idea is you can place it in various conditions and tell it to become a brain cell or a blood cell."

Once the stem cell from the bone marrow is at home in the brain, has it really changed to become a brain cell, or has it just adopted the brain cell's nature? That's a question the current study is designed to answer, Steindler said.

"It may look like a duck and quack like a duck, but it has to really be the duck. We want to make sure a cell can forget where it came from and concentrate on where it's now living," he said.

Joining Steindler in the research are Edward Scott, director of UF's Program in Stem Cell Biology and Regenerative Medicine, and Eric Laywell, a research assistant professor of neuroscience. Initially, the study will be limited to cell cultures and mice. Bjorn Scheffler, a newly recruited UF neuroscientist, will perform the physiological characterization of the stem cells.

Steindler uses the example of a single brain cell with a long axon connecting one part of the brain to another that tells you to remember the smell of your grandma's cookies. If it is a sick cell and a fusion occurs with a stem cell that attaches to it, he said, it still is going to be able to send that message via electrical impulses, but its nature has changed.

"It probably has twice the amount of chromosomes, it could behave funny and might start to do things it is not supposed to do," Steindler said.

"We are getting preliminary data that shows that it appears to be possible to turn these cells into what looks like neural cells, but we are resolving the mechanisms - the molecular factors are necessary to nudge a stem cell down that path," he said.

That will take a few years, he warns, but the results could be worth the wait.

Eventually, Steindler said, we may be able to use the constantly replenished supply of stem cells from our own bone marrow to repair damaged tissue in the brain and elsewhere.

"But first we must understand them, control them, get them to the site of injury or disease and then get them to do their work," he said.

Whether it's a treatment for Parkinson's disease, multiple sclerosis or traumatic brain injury, "people want to hear there is something promising on the horizon," he said.

Sometimes, Steindler said, the science just has to catch up.

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