Development: Brain Cells Reveal Surprising Versatility
by
Gretchen Vogel,
Science News Editor

When a team of scientists reported last year that stem cells from the brains of adult mice could become functional blood cells, many scientists were intrigued, if a bit skeptical. Now, these versatile cells have shown even more surprising abilities: When injected into embryos, it seems, they can develop into nearly every type of tissue in the body. The work, described in the June 2nd issue of Science, leaves a number of questions open. Even so, scientists are amazed at the cells' apparent flexibility.

Generalized Potential of Adult Neural Stem Cells

Diana L. Clarke [1], Clas B. Johansson [1,2], Johannes Wilbertz [1], Biborka Veress [1], Erik Nilsson [1], Helena Karlstrom [1], Urban Lendahl [1], and Jonas Frisen [1]*
Vol. 288, No. 5471, pp. 1660-1663, Science (June 2, 2000).

ABSTRACT:

The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

1. Department of Cell and Molecular Biology, Medical Nobel Institute, and
2. Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden.
* To whom correspondence should be addressed.. E-mail: jonas.frisen@cmb.ki.se

Mouse Neural Stem Cells Grow Tissue
by
Paul Recer,
AP Science Writer

4:11 PM EDT; June 1, 2000; Washington, D.C. (AP) -- Research in mice suggests that stem cells from the adult brain can be nurtured into heart, liver, muscle, and other tissues. This finding may eliminate the ethical dilemma now blocking stem cell studies that utilize human fetal tissues, experts say. The mouse study, by researchers in Sweden, found that neural stem cells taken from the central nervous system of adult mice and transferred to mouse and chicken embryos were converted into the cell types that are found in a variety of body tissues and organs. One part of the study, appearing Friday in the journal Science, showed that some neural stem cells converted to become part of a beating heart in a mouse embryo. Experts said the finding was an important advance in the rapidly developing field of stem-cell research.

"This is a very exciting and interesting result," said Ihor R.Lemischka, a Professor of Developmental Biology at Princeton University. He said if the research can be confirmed in human cells it would "nip in the bud" the moral and ethical concerns that now block Federal funding of human embryonic stem-cell research. Under Federal law, the National Institutes of Health is forbidden to finance human embryo research. After recent stem cell studies, the agency has proposed changing the regulations, but some members of congress oppose the change. The objections to embryonic stem cell research centers on the fact that such cells must be taken from an embryo or a fetus, usually after an abortion, or from frozen human embryos identified as "surplus" at fertility clinics.

It has long been believed that only embryonic stem cells -- which are removed from the unborn -- have the ability to develop into any other cell type in the body. In this process, the embryonic cells change into intermediate stem cells that, in turn, change into other basic cells, such as brain, liver, and heart. Experts believe that eventually stem cells may be used to grow new body parts to replace failing organs, or to treat brain, bone, or blood disorders by replacing diseased cells with healthy ones grown from stem-cell precursors.

Previously, researchers believed that once an embryonic stem cell converted into an organ precursor cell, it could not differentiate into any other type of organ. A neural stem cell, for instance, was thought to be able only to make neurons, astrocytes, or other cells associated with the Central Nervous System (CNS). But the work by scientists at the Karolinska Institute in Stockholm, Sweden, suggests that neural stem cells are able to dedifferentiate into another form of stem cell and then help to develop other organs and not just the brain.

In the study, Swedish scientists separated neural stem cells from adult mouse brains and grew them in large numbers in the laboratory. Stem cells in the culture carried a genetic tag so that they and their descendants could be identified. The cells were then inserted into fertilized chicken eggs or into mouse embryos. A later analysis showed that some of the transplanted stem cells converted into different organ tissues in the developing embryo. The conversion rate of the stem cells was low, 12 percent or less, the researchers reported. "These studies suggest that stem cells in different adult tissues may be more similar than previously thought," the authors report. Jonas Frisen, Karolinska Researcher and senior author of the paper, said "the group does not know what biological signal directs the developmental fate of the neural stem cell." He said "there could be secretions from the developing embryo, but that this was only speculation."

Studies by other researchers have shown that neural stem cells could grow blood tissue, and that blood stem cells could grow neural tissue. A study by Dr. Evan Y. Snyder of Harvard Medical School a year ago showed that neural stem cells could convert into any of the cells needed by an ailing brain. But the Swedish research is the first to suggest that neural stem cells have the ability to grow into a wide variety of organs. "The new work certainly suggests that neural stem cells may be versatile enough to be coaxed down many different development pathways," Snyder said in an interview. He cautioned, however, that "the cells detected in developing organs by Frisen and his colleagues may be part of the nervous structure in the organs." "This could mean that the neural cells retained their original character and did not actually convert over to a new function." Snyder also said that "an important research goal was to find a way to direct and control the evolution of stem cells into other tissue types."

In another paper in Science, Lemischka and his Princeton colleagues report identifying 2,000 genes in blood stem cells. Lemischka said this is an important step toward finding the genes that allow stem cells to differentiate into various tissue types. Lemischka said "finding the genes that help direct cell changes may be key to developing medical therapies using stem cells."

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