STEM CELLS GUIDED DOWN BLOOD’S DEVELOPMENTAL PATHWAY

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STEM CELLS GUIDED DOWN BLOOD’S DEVELOPMENTAL PATHWAY
31 August 2001 - University of Wisconsin-Madison

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 University of Wisconsin-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.

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.

http://www.wisc.edu

About: University of Wisconsin-Madison
In achievement and prestige, the University of Wisconsin-Madison has long been recognized as one of America’s great universities. A public, land-grant institution, UW-Madison offers a complete spectrum of liberal arts studies, professional programs and student activities. Many of its programs are hailed as world leaders in instruction, research and public service.

The university traces its roots to a clause in the Wisconsin Constitution, which decreed that the state should have a prominent public university. In 1848, Nelson Dewey, Wisconsin’s first governor, signed the act that formally created the university, and its first class, with 17 students, met in a Madison school building on February 5, 1849.

From those humble beginnings, the university has grown into a large, diverse community, with about 40,000 students enrolled each year. These students represent every state in the nation, as well as countries from around the globe, making for a truly international population.

UW-Madison is the oldest and largest campus in the University of Wisconsin System, a statewide network of 13 comprehensive universities, 13 freshman-sophomore transfer colleges and an extension service. One of two doctorate-granting universities in the system, UW-Madison’s specific mission is to provide "a learning environment in which faculty, staff and students can discover, examine critically, preserve and transmit the knowledge, wisdom and values that will help insure the survival of this and future generations and improve the quality of life for all."

The university achieves these ends through innovative programs of research, teaching and public service. Throughout its history, UW-Madison has sought to bring the power of learning into the daily lives of its students through innovations such as residential learning communities and service-learning opportunities. Students also participate freely in research, which has led to life-improving inventions from more fuel-efficient engines to cutting-edge genetic therapies.

Students, faculty and staff are motivated by a tradition known as the "Wisconsin Idea," described by UW President Charles Van Hise in 1904 as the compelling need to carry "the beneficent influence of the university ... to every home in the state." The Wisconsin Idea permeates the university’s work and helps forge close working relationships among university faculty and students and the state’s industries and government.

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