Stem cells, forged into neurons, show promise for brain repair

November 30, 2001

MADISON - In a set of meticulous experiments, scientists have demonstrated the ability of human embryonic stem cells to develop into nascent brain cells and, seeded into the intact brains of baby mice, further develop into healthy, functioning neural cells.

In a paper published in the journal Nature Biotechnology (December, 2001), a team of scientists from the University of Wisconsin-Madison, along with colleagues from the University of Bonn Medical Center, show that the blank-slate stem cells taken from early human embryos can, in a laboratory dish, be guided down the developmental pathway to becoming precursor brain cells.

Transplanted into the brains of baby mice, the precursor cells subsequently showed their ability to further differentiate into neurons and astrocytes, the cell species that populate the different regions of the brain and spinal cord.

The work represents a critical step toward a high-stakes payoff for human embryonic stem cell technology - an inexhaustible supply of transplantable neural cells and tissue to repair everything from spinal cord injuries to the ravages of Parkinson's disease. The new work was conducted largely at the WiCell Institute in Madison, Wis., and is now being continued at the UW-Madison Waisman Center.

"This is a very important step. The cells work" as they should, says Su-Chun Zhang, a UW-Madison professor of anatomy and neurology and the lead author of the Nature Biotechnology paper. Co-authors include James A. Thomson and Ian D. Duncan, also of UW-Madison, and Marius Wernig and Oliver Brustle of the University of Bonn Medical Center.

The newly published work is critically important for two reasons: One, it establishes the fact that human embryonic stem cells can be guided down the developmental pathway to becoming brain cells and, two, it shows that they can be transplanted into animals and further develop into the more specific types of cells necessary for normal brain function.

"The neuron that we're seeing after transplant is almost identical to what the neuron should be in the healthy brain," says Zhang. "These are the cells that will be used, ultimately, to treat Parkinson's and other central nervous system disorders."

The human stem cells were transplanted into the brains of newborn mice to co-opt the developmental cues that occur as the animal grows and the brain develops.

"These transplanted cells had no experience in the brain, and we wanted to see if they would mirror the development of the mouse brain," Zhang says. "And they do."

Zhang stressed that the work, in essence, is a demonstration of a system for directing the cells to become the specific types of cells needed for repairing the damaged or ailing brain. Key steps yet to be performed before the technology can be attempted in humans is to assess function and actually treat a condition such as Parkinson's in an animal model such as primates.

"We are nowhere near clinical application," Zhang says. "It will still be some years before we can even try this in people."

However, the new work is strong evidence that human stem cell therapies are likely to live up to their billing as revolutionary treatments for a host of heretofore intractable cell-based diseases.

Moreover, the work performed by Zhang and his colleagues exhibited an important ancillary result: the complete absence of teratomas or tumors in the mice that received the cell transplants. Of concern in any potential stem cell therapy is that tumors may arise from contamination of precursor cells by undifferentiated cells.

"We put a lot of cells, in one instance half-a-million, in a mouse," says Zhang. "The more cells you put in, the more likely you are to have a tumor. The absence of tumors shows our methods for purifying the precursor cells are pretty good."
-end-
Support for the study was provided by the Myelin Project of Washington, D.C. and the Consolidated Anti-Aging Foundation of Naples, Fla.

Terry Devitt (608) 262-8282, trdevitt@facstaff.wisc.edu

University of Wisconsin-Madison

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