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UofL Achieves 'Amazing' Find with Stem Cells
UNGAR LAURA
The Courier-Journal Louisville, KY
13 December 2005


University of Louisville researchers have coaxed stem cells from adult mice to change into brain, nerve, heart and pancreatic cells - a discovery that could lead to treatments for a host of human diseases and possibly end the national debate over the use of embryonic stem cells.

"We have found a counterpart for embryonic stem cells in adult bone marrow. This could negate the ethical concerns," said Dr. Mariusz Ratajczak, leader of the research team and director of the stem -cell biology program at U of L's James Graham Brown Cancer Center.

The next step is to replicate the experiment with similar cells identified in adult humans.

"It's huge," said Ryan Reca, one of the researchers. "It's an amazing discovery."

Others agreed, although they, like Ratajczak, cautioned that it's early in the research process and that more study is needed.

If the cells from adult humans are found to act like those in mice, and other scientists can duplicate the process on a larger scale, the discovery goes from "very important" to "incredibly important," said Dr. Stephen Emerson, chief of hematology/oncology at the University of Pennsylvania, where Ratajczak used to work.

It could lead to expanded research and "be transforming," he said.

"This is a very important first step," said Scott Whittemore, scientific director of UofL's Kentucky Spinal Cord Injury Research Center.

However, Whittemore said that "there are some major issues that need to be resolved before you can think about" translating Ratajczak's research into medical treatments.

Ratajczak announced some of his findings yesterday at the annual meeting of the American Society of Hematology in Atlanta. His team also plans to present a paper today showing that the type of cells it has identified - called "very small embryonic-like," or VSEL - mobilize into the bloodstream to help repair damaged tissue after a stroke in mice.

Although treatments based on the team's discovery are most likely many years off, the research could hold promise for such conditions as heart disease, stroke, diabetes and Parkinson's disease. Using a patient's own VSELs could eliminate the danger of rejection that could exist with donor stem cells.

Some local residents with diseases that could be treated based on the discovery are optimistic.

More immediately, the discovery could boost disease research, said Gayle Zoeller, a 61-year-old Louisville resident with Parkinson's disease.

"I guess we would get a lot more funding," said Zoeller, who has worked with the nonprofit fundraising group Parkinson Alliance. "You wouldn't have to fight Congress."

And the possibility of more research gives her hope.

"The more study that's going on," she said, "eventually something's going to work."

Controversy over cells

Doctors and researchers have been extremely interested in stem cells because they have the potential to develop into many cell types in the body.

Embryonic stem cells are able to give rise to any type of cell except those needed to develop a fetus, according to the National Institutes of Health.

Although the potential for adult stem cells has been thought to be more limited, the use of embryonic stem cells has been controversial because it involves the destruction of embryos, which opponents say amounts to destroying human life.

"Specifically, embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro - in an in vitro fertilization clinic - and then donated for research purposes with the informed consent of the donors," according to a stem -cell primer from the National Institutes of Health.

In 2001, President Bush restricted federal funding of research to existing lines of cells developed from embryos. He cited ethical concerns about the destruction of embryos.

But many researchers and groups have persisted in urging such funding, saying embryonic stem cells hold the best potential for medical research. They also say some of the older stem -cell lines funded under Bush's policy have been contaminated and are not as useful as producing new ones would be.

Ratajczak's recent discoveries show that the newly identified adult cells appear to act like embryonic stem cells. He first described a strategy for identifying and isolating them in a 2004 issue of the journal Leukemia. But that earlier research also showed that VSELs are very rare and difficult to grow in a laboratory.

The research announced yesterday appears to show that VSELs can be grown in the laboratory, multiply into clusters of cells and then be coerced to change into other types of cells, such as brain or heart -muscle cells.

In experiments, the team extracted bone marrow cells from adult mice, put them into a cell sorter to extract the VSELs, put those cells into a petri dish, and then activated them, using a confidential process that is part of a patent application by U of L.

The cells then were exposed to chemicals generated by the mouse's body called "factors" and changed into cardiac muscle cells, pancreatic cells, nerve cells and brain cells.

"We've established how to isolate and how to unleash the power of this cell," said Ratajczak, who has worked at U of L since 2001.

The patent application, made last Thursday, refers to isolating the VSELs, purifying them and unleashing their power.

Dr. Donald Miller, director of the cancer center, would not say how much money went into Ratajczak's research - although he did say that the university "invested heavily" to bring Ratajczak's team to Louisville and that the group received two National Institutes of Health grants to support research in the past six months.

"This is an early observation, but we're terribly excited about it and what it means in the future," Miller said. "It certainly has potential for many types of diseases."

Wide implications

A spokeswoman for the National Institutes of Health said the chairman of the agency's stem -cell task force would not comment on Ratajczak's research because he has not had a chance to study it.

But others agreed the discovery could have wide-ranging implications - especially if VSELs in humans can do what VSELs in mice have been made to do.

"It would certainly be very exciting to be able to transform them, convert them into other cells. It might diminish the demand for embryonic stem cells," said Arthur Caplan, a University of Pennsylvania bioethicist.

But he added: "Place your bets on all forms of research right now. It's too soon to say that adult stem cells can do what embryonic cells do."

In the meantime, Benjamin Kirby, communications director for the Parkinson's Action Network, said he would like to see the federal government end restrictions on funding for embryonic stem-cell research.

"I would applaud any breakthrough that came from adult stem cells or embryonic stem cells, and we would urge continued funding of both tracks of research so we can have more breakthroughs like this," said Kirby, whose network is a Washington, D.C.-based advocacy and lobbying agency.

As he continues his work, Ratajczak said he hopes the recent discovery becomes a foundation for other researchers.

"Everybody can repeat this procedure," he said. "We're interested in as many laboratories as possible to go in our footsteps."

Laura Ungar can be reached at (502) 582-7190.

Staff writer Peter Smith contributed to this story.

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RESEARCH HIGHLIGHTS

University of Louisville researchers have caused cells from adult mice to change into brain, heart -muscle, pancreatic and nerve cells. The adult cells seem to mimic embryonic stem cells.

The research could lead to therapies for stroke and Parkinson's disease, among other things. If other scientists repeat the process on a larger scale, it could reduce the need for embryonic stem cells. It could also eliminate rejection problems that can exist when using stem cells from a donor.

Although research is in the early stages, it eventually could end the national controversy over the use of embryonic stem cells.

On the Web

Participate in an online forum on stem-cell research at courier-journal.com.

About stem cells

National Institutes of Health:
http://www.stemcells.nih.gov

Stem Cell Research Foundation:
http://www.stemcellresearchfoundation.org

American Association for the Advancement of Science:
www.aaas.org/spp/sfrl/projects/stem/main.htm

INFORMATIONAL GRAPHIC; EMBRYONIC-LIKE ADULT STEM CELL BY THE COURIER JOURNAL (SEE LIBRARY MICROFILM OR LIBRARY KIOSK PDF PAGES)

Caption: Courtesy of University of Louisville/Brown Cancer Center

Dr. Mariusz Ratajczak, director of the stem-cell biology program at the University of Louisville's James Graham Brown Cancer Center, led the research team. The experiment now must be replicated with similar cells identified in adult humans.

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