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."