June 2, 2000 Washington D.C. -- Reprogrammed adult neural stem cells can potentially generate a cornucopia of cell types-giving rise to cells in heart, liver, muscle, intestine and other tissues, a 2 June Science study suggests.
When adult neural stem cells from mice are grown with embryonic cells or within an embryo, the adult stem cells can revert to an unspecialized state and give rise to different cell lineages, according to the Science study. The research, completed by a team of Swedish scientists, adds to a growing body of data indicating that adult stem cells, like embryonic stem cells, may be more versatile than previously assumed.
Embryonic stem cells are the "blank slates" of an organism, capable of developing into all types of tissue in the body. Scientists have long been interested in the therapeutic potential of embryonic stem cells, which may be used someday to create new tissues for organ transplants and replacements for cells destroyed by diseases like diabetes or trauma like spinal cord injuries.
As ethical and legal controversy threatens to cloud the future of embryonic stem cell research, however, some scientists have turned to adult stem cells to discover whether they also have the same open-ended potential. Until recently, researchers thought that the more specialized adult stem cells, found in areas of the body like the skin, nervous system, and blood and lymph systems, could only give rise to their own kind. Now, scientists are accumulating evidence--including last year's mouse study showing how brain stem cells transplanted into bone marrow could produce blood cells (see Science, 22 January 1999)--that adult stem cells may be capable of reprogramming themselves.
The Science study confirms that adult stem cells are in fact more chameleon-like than previously suspected, taking cues from their cellular environment to produce offspring of the same type as the cells that surround them. To test the influence of environment on adult stem cell destiny, the Swedish team exposed genetically tagged mouse neural stem cells to a variety of tissue types by growing them together with embryo cell cultures in the lab and injecting them into early-stage chick and mouse embryos.
In the lab cultures, the offspring of the stem cells switched their identities to become muscle cells. Depending on which early cell layer they managed to infiltrate in the developing chick and mouse, the stem cell progeny incorporated into these embryos contributed to heart, lung, intestine, kidney, liver, nervous system, and other tissues.
As the researchers discovered, even lone neural adult stem cells displayed this ability to differentiate themselves into various cell types. In all these cases, the cells looked and acted just like the host cells around them. The "most striking indications" of this complete cellular makeover, say the authors, were the apparently normal and beating embryonic mouse hearts containing very large amounts of these derived stem cells.
Although the scientists are certain that environment plays a major role in determining an adult stem cell's fate, they aren't entirely sure what critical factor environment supplies.
"The short answer is that we have no clue," says co-author Jonas Frisén of the Karolinska Institute in Stockholm. "We can speculate that the crucial elements are extracellular signals, or secretions from the embryonic cells. There is probably a cocktail of various factors involved, but we have no solid data yet about what these molecules are."
If scientists can determine the molecular composition of these extracellular signals, Frisén says, researchers could take the next step and coax these adult stem cells toward several different cellular lineages, without exposing them to embryonic cells at all.
Frisén and colleagues want to test other types of adult stem cells, not just neural cells, to see if they have similarly plastic potential.
"This could be very valuable in a clinical setting, since neural stem cells are really the least accessible," says Frisén.
The research team is also planning future experiments to see how long the transformed stem cells survive within these tissues, and whether they retain their new commitments indefinitely.
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