Lucky or Good? Stem cells' all-around talent disputed (Stem cells)
Authors: Davenport R. John 
Published: August 2003

Winning the lottery could change your life, but if the odds are 1 in 10 million, is it worth buying a ticket? A new study questions the gamble of trying to turn brain stem cells into blood cells. Although previous work suggested that this switch occurs frequently, the current results hint that those observations might have been a fluke. Two additional papers put forth an alternative explanation for how adult stem cells appear to pick up characteristics of unrelated tissues.

Stem cells are coveted for their versatility. Adult stem cells from, say, the brain can mature into any of the cell types that make up that organ. Several studies suggest that adult stem cells boast even more impressive gifts as well: They can morph into cells from different tissues. Such power could be a boon for treatment of disease. If adult stem cells could rejuvenate multiple parts of the body, scientists could circumvent the moral dilemma of using embryonic stem cells--cells from the early embryo that can mature into any kind of tissue. In 1999, developmental biologist Christopher Bjornson and colleagues isolated neural stem cells and cultivated them in the lab. They discovered that the cells could turn into blood cells when injected into animals. In the new work, a different team investigated whether the brain stem cells' flexibility was intrinsic or depended on changes that occurred while they were being raised outside the body.

To explore this question, Morshead and colleagues prepared neural stem cells from mice that produced a marker protein and grew the cells in broth. They then irradiated mice that did not carry the marker protein--to kill most of the animals' blood cells--before injecting the tagged neural stem cells. Several months later, the researchers examined the bone marrow, where blood cells mature, from 104 recipient animals. They did not find any blood cells that carried the marker protein, regardless of how long the stem cells had grown in the lab before injection. The results indicate that the neural stem cells had not made the switch.

Although the neural stem cells didn't become blood cells, they did change their behavior while growing in culture. Over time, they divided more quickly, became stickier, and stopped requiring the presence of growth factors to survive. These alterations, say the authors, might reflect mutations acquired in the lab. Bjornson's results could have arisen from similar, rare genetic changes that allow brain cells to become blood cells, Morshead and colleagues suggest in their paper.

The work stokes the debate about the pliability of stem cells. "It doesn't say that neural precursor cells cannot possibly develop into blood cells," says neurologist David Greenberg of the Buck Institute for Age Research in Novato, California. But the results suggest that converting from brain into blood is uncommon. "It comes down to an issue of frequency," says Greenberg. But Bjornson, who is now at the University of Washington, Seattle, says the two studies might not be comparable. Because his cultured cells didn't display the changes reported in the new work, "it's pretty clear to me that [Morshead and colleagues are] injecting different cells."

Two reports in
Nature
also raise concerns about adult stem cells' purported breadth of aptitude. Separate research teams showed that, at least in a petri dish, adult stem cells can fuse with and take on characteristics of embryonic stem cells. The authors suggest that similar cellular unions could explain how marker proteins from adult stem cells of one type end up in different tissues. Whether this phenomenon occurs in animals remains to be tested, but it's clear that researchers will need more evidence before we know if stem cell plasticity will pay out on its tantalizing jackpot.

--R. John Davenport; suggested by Amir Sadighi Akha

C. M. Morshead, P. Benveniste, N. N. Iscove, D. van Der Kooy, Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations.
Nat. Med.
8
, 268-273 (2002).
[Abstract]
[Full Text]

N. Terada, T. Hamazaki, M. Oka, M. Hoki, D. M. Mastalerz, Y. Nakano, E. M. Meyer, L. Morel, B. E. Petersen, E. W. Scott, Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion.
Nature,
13 March 2002 [e-pub ahead of print].
[Abstract]
[Full Text]

Q.-L. Ying, J. Nichols, E. Evans, A. G. Smith, Changing potency by spontaneous fusion.
Nature,
13 March 2002 [e-pub ahead of print].
[Abstract]
[Full Text]

Further Reading

• C. R. R. Bjornson, R. L. Rietze, B. A. Reynolds, M. C. Magli, A. L. Vescovi, Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo.
Science
283
, 534-537 (1999).
[Abstract]
[Full Text]

• E. Strauss, Brain stem cells show their potential.
Science
283
, 471 (1999).
[Abstract]
[Full Text]

• G. Vogel, Studies cast doubt on plasticity of adult cells.
Science
295
, 1989-1991 (2002).
[Abstract]
[Full Text]