Jefferson researchers have early evidence of bone marrow stem cells able to become brain cells

November 11, 2001

Using a potion of growth factors and other nutrients, scientists at Jefferson Medical College have shown in the laboratory they are able to convert adult human bone marrow stem cells into adult brain cells.

While it's early in the research, the results suggest such stem cells may have potential use in someday treating neurodegenerative diseases such as Parkinson's disease.

"The goal [of the work] is to find stem cells that we can differentiate into dopamine neurons to replace those lost in Parkinson's disease," says developmental biologist Lorraine Iacovitti, Ph.D., professor of neurology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, who leads the research.

She reports her team's findings November 11 at the annual meeting of the Society for Neuroscience in San Diego.

Human adult bone marrow stem cells - also known as pluripotent stem cells - normally give rise to human bone, muscle, cartilage and fat cells. Embryonic stem cells, in contrast, can become any type of cell.

Other scientists have shown previously that at least a portion of mouse bone marrow stem cells treated with various growth factors and other agents will go on to resemble neurons in cell culture.

Dr. Iacovitti's team used the previous group's cocktail of growth factors and nutrients on human bone marrow stem cells and found that only some cells converted to neurons - that is, they looked like neurons in that they developed "cellular processes."

But by experimenting with different combinations of growth factors and nutrients, they eventually found a cocktail of reagents that converted 100 percent of cells within an hour - a stunning development that had never been shown before.

"It flew in the face of everything I knew from developmental biology," Dr. Iacovitti says. "We've identified factors that get 100 percent of adult human bone marrow stem cells converted to neurons very quickly." Not only do the converted cells look like neurons, she says, they contain neuronal proteins.

The converted stem cells have neuronal markers and markers that are identified with subclasses of neurons. "That's important because we've shown they can convert to specific classes of neurons. We have seen serotonin and GABA enzyme neurons. We want to get them to convert to dopamine neurons, which we haven't seen yet." Adult human bone marrow stem cells have advantages as sources of cells.

"The major advantage of using adult human bone marrow stem cells is that each person can be his own donor, meaning they can have an autologous graft of cells without rejection," Dr. Iacovitti says. "The hope is that we won't have to use embryonic stem cells and aborted fetuses for stem cell lines."

There is one caveat, she notes. To date, the new neurons revert back to their original undifferentiated state in two to three days. "The bigger problem to solve is how to keep them differentiated," she says. A key, she says, may lie in understanding what occurs in the growth media in which the stem cells incubate for several days and into which they release certain growth factors.

If the "conditioned" growth media plays a role in the conversion to neurons, the researchers "hope to find ways to remove the stem cells from the culture - which is difficult - and differentiate them into what we want." The next step, she says, will be for her team to both better understand the stem cell conversion in the laboratory and to study the process in animals.
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Thomas Jefferson University

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