Stem Cells: 5 Year Progress Report

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Stem cell:
A cell that can change into other types.

Embryonic stem (ES) cell:
Cell from embryo, can become any cell type.

Adult stem cell: Stem cell from mature animal, often from bone marrow.

Differentiation: Process of becoming more specialized.

Is politics or science driving the interest in adult stem cells?

Scientific see-saw
Biologists have long known that some cells must be changing form -- dividing into more specialized cells -- as a multi-cellular organism grows from a fertilized egg to the billions of cells in a mature naked mole rat or developmental biologist. Some of the first stem cells, discovered in bone marrow, differentiate into all kinds of blood cells. Though they struggle with an unpronounceable handle, these "hematopoietic" stem cells are the active ingredient in a popular cancer treatment, the bone marrow transplant.

Diagram shows stem cells becoming other types of cells.
Hemapoietic stem cells, derived from the bone marrow, give rise to all types of blood cell.
Graphic: NIH

(Improved techniques now allow bone marrow transplant doctors to isolate hematopoietic stem cells from blood. That's much easier on the donor than the older procedure, poking dozens of holes in bones to extract marrow. In other words, adult stem cells already have a clinical use.)

In the years since the 1998 announcement on human ES cells, researchers have described startling results from two other types of adult stem cells, also originating in bone marrow. Mesenchymal stem cells seem able to form specialized cells in the nervous system, muscle, liver, kidney and elsewhere. (We'll return to the third type on the next page.)

The idea that adult stem cells were so flexible flouted biology's conventional wisdom, since healthy cells were considered to be trapped on a one-way path toward greater differentiation. Healthy cells, in other words, don't get less specialized -- they get more specialized. (Cancer cells, however, do get more primitive as they reproduce. For more on the issue, see "Flexible Arrangement ..." in the bibliography).

One part science, one part politics?
A second reason for the widespread skepticism about adult stem cells is the political backdrop: Many who oppose embryonic stem cell research on ethical or religious grounds would love to find a less-objectionable replacement cell. ("Politicians are already keenly interested in results from Catherine Verfaillie, director of the Stem Cell Institute at the University of Minnesota -- as a way to put ES cells out of business," reported Science last year.) Verfaillie, who, as we'll see shortly, has assembled good evidence for change, or plasticity, in adult stem cells, told the legislators it was "too soon to draw any conclusions" (see "Plasticity..." in the bibliography).

Splashes of blue in sea of spindly green cells.Spinal cord neurons developed when ES cells were cultured for five days. The differentiation into neurons was monitored using antibodies, and by profiling the expression of genes and proteins. Neurons also may be derived from adult stem cells. Photo: Courtesy Alexander K. Murashov, East Carolina University School of Medicine.

At any rate, as the adult cell wave crested, researchers discovered that some of the stem cells were not becoming specialized cells but rather fusing with them. That meant the markers on the outside of specialized cells, which supposedly proved their descent from adult stem cells, actually indicate that the cell was a hybrid, with two nuclei.

Fusion was just one source of confusion. Researchers have also attributed some erroneous markers erroneous markers to mutations. And when a cell takes up DNA from another cell, as some immune cells do while "eating" foreign cells, they will contain foreign DNA, at least temporarily.

Can anybody make sense of human stem cell research?

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