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RESEARCH

Stem cells guided down blood’s
developmental pathway


by Terry
Devitt

 

For the first time, scientists have demonstrated that undifferentiated
human embryonic stem cells can be teased down a developmental pathway
to become blood cells.

The work, conducted by a team of researchers at the UW-Madison, is
important because it demonstrates the potential for creating in the
laboratory a novel source of blood cells for transplantation and
transfusion. The work was reported today, Sept. 3, in the Proceedings
of the National Academy of Sciences (PNAS).

Finding out how to direct embryonic
stem cells
— blank-slate cells that arise at the earliest stages
of development, to become blood, bone, skin, nerve and other cell
types — is one of the biggest technical challenges facing scientists
as they work to advance stem cell technology. Learning how blood
arises from embryonic stem cells has been a fundamental question in
biology.

The accomplishment reported by the Wisconsin scientists shows that
undifferentiated stem cells can be coaxed to become primitive types of
blood cells that later develop into more mature types of blood cells
that, one day, may be used for transfusion or transplant technologies.

"These results show an effective and efficient way to derive
blood cells from these early precursors," says Dan Kaufman, a
hematology fellow at the UW-Madison Medical School and the lead author
of the PNAS paper.

Kaufman emphasizes that while the work shows great promise toward
the ultimate goal of taming embryonic stem cells in the lab, the work
reported today still represents early-stages of the science and that
clinical application remains years in the future.

The new research, however, holds promise for illuminating the
process of human development as generic embryonic cells begin down
developmental pathways to become any of the 220 types of cells and
tissue that make up the human body.

Moreover, the ability to create supplies of blood in the lab has
obvious implications for augmenting human blood supplies for
transfusion and for transplant therapies to treat cancers of the blood
and bone marrow such as leukemias and myelomas.

"This is not something that’s going to be available tomorrow
or next year," Kaufman says, but the research does represent a
key step forward in the quest to direct stem cells to become a
specific cell type.

Writing in PNAS, Kaufman and his colleagues show that stem cells
can be directed to become what are known to scientists as
hematopoietic precursor cells (or hematopoietic colony-forming cells),
cells that display distinct biochemical markers and gene products
characteristic of blood and bone marrow cells in the body. Moreover,
these precursor cells go on to form colonies of white blood cells, red
blood cells and platelets, cells identical to those that arise from
human bone marrow.

If perfected, the technology could significantly improve human
blood supplies.

"There is generally a shortage of blood," says Kaufman,
and if the technology matures it "may one day be possible to
augment that blood supply."

The work at Wisconsin was accomplished in tissue culture by
exposing undifferentiated stem cells to bone marrow and other cells as
well as growth factors in order to encourage them down the
developmental pathway to becoming blood.

The need for certain kinds of blood cells for transplant is acute.
According to Kaufman, only about 25 percent of patients who need blood
or bone marrow transplants from another person to treat leukemias and
other cancers get those transplants. "A goal," he says,
"would be to better treat those remaining 75 percent" of
patients unable to get transplants for lack of well-matched donor
cells.

There are about 20,000 bone marrow transplants conducted annually
in the United States to treat leukemias and other diseases. In humans
and other animals, blood is constantly renewed in bone marrow and
marrow transplants have proved to be an effective way of treating
blood and bone cancers.

In addition to Kaufman, the Wisconsin team included Eric T. Hanson,
Rachel L. Lewis, Robert Auerbach and James A. Thomson. The work was
supported in part by a grant from the Wisconsin Comprehensive
Cancer Center
and used facilities supported by the WiCell
Research Institute
, a private institute devoted to human embryonic
stem cell research supported by the Wisconsin
Alumni Research Foundation
.

(View
a full news release version of this story
)

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