When Brain Becomes Blood

For this article, Eugene Russo interviewed Christopher R.R. Bjornson, a graduate student in the department of biochemistry at the University of Washington in Seattle. Data from the Web of Science (ISI, Philadelphia) show that Hot Papers are cited 50 to 100 times more often than the average paper of the same type and age. 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, 283:534-7, Jan. 22, 1999. (Cited in 150 papers) In 1998, a fledgling stem cell biotech venture called NeuroSpheres Ltd. narrowly missed a lucrative window of opportunity. In June of that year, the Calgary-based company went out of business, due in part to dwindling venture capital. Just a few months later, published findings by Johns Hopkins University professor John Gearhart and University of Wisconsin professor James Thomson helped precipitate interest in stem cell research, making the field one of the most attractive investments in biotech.1-3 But just before NeuroSpheres went under, it too finished a stem cell study that would add excitement to the stem cell research field. The now disbanded NeuroSpheres laboratory team showed that in mice, neural stem cells (NSCs) could become hematopoietic cells in vivo. According to lead author Christopher R. R. Bjornson, now a biochemistry graduate student at the University of Washington, the NeuroSpheres researchers noted a few instances in which certain cells would express traits of other cell lineages.4 "From that we started to really question ... whether or not stem cells were only confined to a certain subset of fates," he explains. To test this concept, he and his colleagues first irradiated mice to eliminate most of the animals' endogenous hematopoietic precursors. A key step, says Bjornson, was using a sub-lethal dose of radiation rather than lethal doses, which often are used for bone marrow (BM) transplants. They correctly reasoned that the NSCs would take longer than BM cells to become hematopoietic and they did not want the mice to degenerate too quickly. Then, they injected clonally derived NSCs into the mice's tail veins and waited. Within 22 weeks, researchers detected donor-derived cells in the peripheral blood of NSC recipient animals. They found positive cell engraftment in all of the BM control mice and embryonic NSC mice, 70 percent of the adult NSC mice, and 63 percent of the clonal-adult NSC recipients. "We were using an assay that had been used repeatedly in the hematopoietic field as one that would reliably test the [stem cell potential] of bone marrow derived stem cells," Bjornson comments. Despite the NeuroSpheres investigators' success in using an in vivo mouse assay, replicating the experiment in vitro has proven difficult: they still do not know the factors and extracellular stimuli--and their combination--that will make NSCs assume a hematopoietic identity. "It's still an enormous black box," says Bjornson. He and his colleagues failed to find the right recipe of cytokines and extracellular matrix molecules to coax the cells to convert in vitro; their experiments were truncated prematurely because of NeuroSpheres' demise. Bjornson notes that the 1999 findings are part "proof-of-principle" and part practical application. No previous research had definitively shown such plasticity in these cell populations. In a more practical sense, the findings potentially could overcome a limitation in this and other fields: Unlike many stem cells, NSCs can expand in vitro to produce the desired number of cells. However, such an application might be moot as investigators continue to find ways to push stem cells into several different lineages. Despite its lack of clear practical value, the paper has been highly cited. Bjornson suggests that scientists might be justifying their studies with the NeuroSpheres work or drawing parallels between stem cell biology and developmental biology. Also, clinicians and bioethicists could be citing the paper because the research involved adult stem cells, as opposed to the ethically volatile embryonic stem cells. According to Bjornson, stem cell researchers will have to decide what experiments need to be done to confirm that stem cell transdifferentiation is a real phenomenon. That is, says Bjornson, they'll have to show that it's not "hocus pocus." It was not something, he says, that his team was "pushing on the system." Eugene Russo can be contacted at erusso@the-scientist.com References 1. R. Lewis, "Embryonic stem cells debut amid little media attention," The Scientist 11[19]:1, Sept. 29, 1997. 2. J.A. Thomson et al., "Embryonic stem cell lines derived from human blastocysts," Science 282:1145-7, 1998. (Cited 210 times) 3. M.J. Shamblott et al., "Derivation of pluripotent stem cells horn cultured human primordial germ cells," Proceedings of the National Academy of Sciences, 95:13726-31, 1998. (Cited 130 times) 4. S. Tajbakhsh et al., "A population of myogenic cells derived from the mouse neural-tube," Neuron, 13:813-21, 1994.

When Brain Becomes Blood

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