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Contact: Claire Bowles
claire.bowles@rbi.co.uk
44-207-331-2751
New Scientist

Is this the cell that could revolutionise medicine?

IT MIGHT turn out to be the most important cell ever discovered. It's a stem cell found in adults that can turn into every single tissue in the body.

Until now, only stem cells from early embryos were thought to be able to do this. If the finding is confirmed, it will mean cells from your own body could one day be turned into all sorts of perfectly matched replacement tissues and even organs.

If so, there would be no need to resort to therapeutic cloning-cloning people to get matching stem cells from the resulting embryos. Nor would you have to genetically engineer embryonic stem cells (ESCs) to create a "one cell fits all" line that doesn't trigger immune rejection. The discovery of such versatile adult stem cells will also fan the debate about whether embryonic stem cell research is justified.

"The work is very exciting," says Ihor Lemischka of Princeton University. "They can differentiate into pretty much everything that an embryonic stem cell can differentiate into."

The cells were found in the bone marrow of adults by Catherine Verfaillie at the University of Minnesota. Extraordinary claims require extraordinary proof, and though the team has so far published little, a patent application seen by New Scientist shows the team has carried out extensive experiments. These confirm that the cells-dubbed multipotent adult progenitor cells, or MAPCs-have the same potential as ESCs. "It's very dramatic, the kinds of observations [Verfaillie] is reporting," says Irving Weissman of Stanford University. "The findings, if reproducible, are remarkable."

At least two other labs claim to have found similar cells in mice, and one biotech company, MorphoGen Pharmaceuticals of San Diego, says it has found them in skin and muscle as well as human bone marrow. But Verfaillie's team appears to be the first to carry out the key experiments needed to back up the claim that these adult stem cells are as versatile as ESCs.

Verfaillie extracted the MAPCs from the bone marrow of mice, rats and humans in a series of stages. Cells that don't carry certain surface markers, or don't grow under certain conditions, are gradually eliminated, leaving a population rich in MAPCs. Verfaillie says her lab has reliably isolated the cells from about 70 per cent of the 100 or so human volunteers who donated marrow samples.

The cells seem to grow indefinitely in culture, like ESCs. Some cell lines have been growing for almost two years and have kept their characteristics, with no signs of ageing, she says. Given the right conditions, MAPCs can turn into a myriad of tissue types: muscle, cartilage, bone, liver and different types of neurons and brain cells. Crucially, using a technique called retroviral marking, Verfaillie has shown that the descendants of a single cell can turn into all these different cell types-a key experiment in proving that MAPCs are truly versatile.

Also, Verfaillie's group has done the tests that are perhaps the gold standard in assessing a cell's plasticity. She placed single MAPCs from humans and mice into very early mouse embryos, when they are just a ball of cells. Analyses of mice born after the experiment reveal that a single MAPC can contribute to all the body's tissues.

MAPCs have many of the properties of ESCs, but they are not identical. Unlike ESCs, for example, they do not seem to form cancerous masses if you inject them into adults. This would obviously be highly desirable if confirmed.

"The data looks very good, it's very hard to find any flaws," says Lemischka. But it still has to be independently confirmed by other groups, he adds.

Meanwhile, there are some fundamental questions that must be answered, experts say. One is whether MAPCs really form functioning cells. Stem cells that differentiate may express markers characteristic of many different cell types, says Freda Miller of McGill University. But simply detecting markers for, say, neural tissue doesn't prove that a stem cell really has become a working neuron.

Verfaillie's findings also raise questions about the nature of stem cells. Her team thinks that MAPCs are rare cells present in the bone marrow that can be fished out through a series of enriching steps. But others think the selection process actually creates the MAPCs. "I don't think there is 'a cell' that is lurking there that can do this. I think that Catherine has found a way to produce a cell that can behave this way," says Neil Theise of New York University Medical School.

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Author: Sylvia Pagan Westphal, Boston

New Scientist issue: 26th January 2002

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