Ultimate Stem-Cell Discovered
Sylvia PagánWestphal

January 23, 2002; Boston, MA ( New Scientist) -- A stem cell has been found in adults that can turn into every single tissue in the body. It might turn out to be the most important cell ever discovered. Until now, only stem cells from early embryos were thought to have such properties. 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. Furthermore, 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 does not 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."

Findings So Remarkable that Extraordinary Claims Require Extraordinary Proof

The cells were found in the bone marrow of adults by Prof. Catherine Verfaillie at the University of Minnesota.Though the team has published little so far, a Patent Application seen by staff at the New Scientist shows the Minnesota 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 Prof. 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 do not carry certain surface markers, or do not 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 percent of the 100 or so human volunteers who donated marrow samples.

Indefinite Growth

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 aging," 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.

Fundamental Questions

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 does not prove that a stem cell really has become a working neuron. [ Editor's Note: On electrophysiological testing, can one demonstrate that the cells have a voltage-gated potassium and sodium channels, which are essential components of true neurons? In short, these cells may have neuronal surface markers but not be neurons in the strictest sense.]

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 [What?]. "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. [What? "Show me the data!"]