Adult Cells Undergo Identity Switch Reported In Science

January 22, 1999

Washington D.C. - Research by a group of Italian and Canadian scientists indicates that certain adult cells-previously assumed to be permanently wedded to their specialized roles in the body-can shed their identities and reinvent themselves as different types of cells. In the study, reported in the 22 January issue of Science, the authors transplanted adult stem cells from the brains of adult mice into the bone marrow of new mice, where the stem cells changed their behavior and began generating blood cells. The findings raise the possibility that in the future adult stem cells could be used to supply a variety of new cells for important therapeutic uses, for example to generate healthy blood cells for treating patients with blood disorders.

Researchers recently proposed that using stem cells to grow healthy tissues was one of several beneficial applications for their new-found ability to grow human stem cells from early-stage embryos, a finding announced in Science last November. Embryonic stem cells are primordial cells that divide indefinitely and give rise to the body's different cell types as they develop. However, although these cells may have the potential to provide considerable benefits, they also pose some controversial ethical implications because they come from human embryos.

Now, a study on mice by Angelo Vescovi, of NeuroSpheres Limited in Canada and the National Neurological Institute in Italy, and his colleagues suggests that stem cells don't have to come from embryos in order to generate specialized cells. "We went the other way around and used adult stem cells instead," said Vescovi.

Adult stem cells are more specialized than the primitive stem cells of an early embryo. These stem cells supply new cells to parts of the body with a high cellular turnover rate, such as the hematopoeitic (blood producing) system, the intestines, or the skin. In their experiment, Vescovi and his colleagues used neural stem cells (NSCs) from the central nervous system of mice. NSCs generate the major cell types found in the adult brain, namely neurons and their support cells.

The authors injected the NSCs into a second group of mice whose hematopoietic stem cells (these cells reside primarily in the bone marrow where they produce the different varieties of blood cells) had been destroyed by a near-lethal dose of radiation. Once in the blood stream, the NSCs seeded the mice's bone marrow (and the spleen, another site of blood production). There, they took over the job of the hematopoietic stem cells and churned out a fresh supply of blood cells. Apparently, during their development as NSCs, the stem cells had not undergone any irrevocable changes that made them unable to specialize as other types of stem cells as well.

"It took us a while to believe our own data. The tissue of the body has always been seen as unchangeable," Vescovi said.

Vescovi and his colleagues speculate that it may be possible in the future to perform bone marrow transplants using adult stem cells to create a new supply of healthy blood in patients with cancers of the hematopoietic system such as leukemia. To reach that point, however, researchers will have to confirm that human stem cells behave the same way the mouse stem cells do. And they will have to accomplish the daunting task of isolating and growing adult human stem cells.

More directly, the evidence from Vescovi and his colleagues' study indicates that neural stem cells, or "NSCs," were able to revert to their unspecialized, embryonic state and then re-specialize as hematopoietic stem cells. To further investigate whether this process was in fact occurring, the researchers also injected a second group of irradiated mice with foreign hematopoietic stem cells. Because these cells had been producing blood cells originally, it took them less time to produce blood cells after being transplanted than it did the NSCs. The NSCs may have taken more time because they had to first "unlearn" their original tasks.

In their paper, Vescovi's group notes that their results are consistent with a key finding by Ian Wilmut and his colleagues, who announced the success of their cloning experiments in 1997. In both cases, adult cells returned to their primordial states and then began new lives; one became Dolly the sheep, the other a blood producing stem cell.
-end-
ORDER ARTICLE #16: "Turning Brain into Blood: A Hematopoietic Fate Adopted by Adult Neural Stem Cells in Vivo," by C. R. R. Bjornson, R. L. Rietze, B. A. Reynolds, and A. L. Vescovi at NeuroSpheres Limited in Calgary, Canada; C. R. R. Bjornson is currently at U. of Washington in Seattle, WA; R. L. Rietze is currently at The Walter and Eliza Hall Institute of Medical Research in Victoria, Australia; M. C. Magli at Institute for Mutagenesis and Differentiation in Pisa, Italy; A. L. Vescovi is also at National Neurological Institute "C. Besta" in Milan, Italy. CONTACT: Angelo L. Vescovi at 39-0223-942-72 (phone), 39-0335-6841-857 (cellular phone), 39-0223-942-72 (fax), or vescovi@tin.it (e-mail)

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