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Murray has done a super job finding and sending to the list these articles on stem cell research. Be sure and read these postings to learn what's happening in this exciting area. Thanks, Murray! Jeanette Fuhr 50/47/44? ----- Original Message ----- From: "Murray Charters" <[log in to unmask]> To: <[log in to unmask]> Sent: Saturday, November 25, 2000 12:12 AM Subject: 2.) Stem Cells Tapped to Replenish Organs - Brain The Scientist 14[23]:20, Nov. 27, 2000 http://www.thescientist.com/yr2000/nov/research_001127.html Brain Goal: To replace neurons that have died as a result of degenerative diseases or stroke. Ronald D.G. McKay and his Laboratory of Molecular Biology at the National Institute of Neurological Disorders and Stroke can efficiently generate dopaminergic and serotonergic functional neurons in vitro from mouse ESCs.2 They can get ASCs, in the form of mesencephalic precursor cells, to induce functional recovery when transplanted into parkinsonian rats.3 But according to McKay, these ASCs stop generating dopaminergic neurons in culture after a week or so. The yield improves if the cells are grown under low-oxygen conditions, which are characteristic of the fetal environment.4 Still, McKay notes that his lab's experience thus far with several types of ASCs is that "they don't turn into dopaminergic neurons with any kind of efficiency." Referring to a 1999 paper from the Karolinska Institute that reported such a result,5 he wonders whether the final yield is "really a dopaminergic cell or not." One problem besetting such research is the uncertain identity of ASCs in the mammalian brain. Last year, a Karolinska team led by Jonas Frisén announced that the ependymal cells lining the brain's ventricles were neuronal ASCs.6 Five months later, a Rockefeller University group headed by Arturo Alvarez-Buylla countered that subventricular zone (SVZ) astrocytes were the true neuronal ASCs. This group also rejected the ependymal-cell hypothesis after finding that those cells neither formed neurospheres, nor accumulated nucleoside labels, as they would if they divided.7 The New York Times ran a story on the ensuing brouhaha.8 Alvarez-Buylla, who just moved to the neurosurgery department of the University of California, San Francisco, says that the conflict may arise, in part, because SVZ astrocytes "interact very, very closely with the ependymal cells." But he maintains that ependymal cells only serve to create a niche where neurogenesis can occur. His lab is currently examining two signaling systems that seem to prompt SVZ astrocytes into becoming neurogenic.9 Last June, Frisén bolstered his theory with a paper showing that neural stem cells had broad differentiation potential.10 The authors couldn't verify that most of their experiments actually involved ependymal cells. But when ependymal-cell-derived neurospheres were injected into the amniotic cavities of chick embryos, the cells showed broad differentiation potential (the data, at footnote 16, weren't published). Frisén now says he has additional, unpublished lines of evidence indicating that ependymal cells are neural stem cells. His theory may need that support. Derek van der Kooy and his colleagues at the University of Toronto weren't able to get ependymal cells to make neurons in vitro.11 A similar negative finding appears in an upcoming paper describing a study led by Eric D. Laywell and Dennis A. Steindler, professors of anatomy and neurobiology at the University of Tennessee in Memphis.12 They and their colleagues, on the other hand, confirmed Alvarez-Buylla's hypothesis by observing that SVZ astrocytes could give rise to neurons, as identified by the expression of ß-III tubulin and other markers. (Functional studies of the neurons are now under way.) In a significant extension of that hypothesis, they found that astrocytes from cerebral cortex, cerebellum, and spinal cord could also turn into neurons--but only if the astrocytes were derived in the first two postnatal weeks. "This correlates with what we believe to be the maturation of the astrocyte in the nervous system," notes Steindler. "The end of this critical period in astrocyte multipotency coincides with the end of a period in which the brain's regenerative responses are far more successful than those in the more mature brain."