http://www.news.wisc.edu/view.html?get=6866
Posted 11/30/01
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 UW-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,
and is being continued at the 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."
Support for the study was provided
by the Myelin Project of Washington, D.C., and the Consolidated Anti-Aging
Foundation of Naples, Fla.
Copyright © 2001 The Board of
Regents of the University of Wisconsin System
by Terry Devitt