Friday, November 9, 2007

[StemCells] SCs & brain repair

UCSF stem cell study reveals cells' capability in mouse brain tissue
repair
UCSF scientists have determined that adult stem cells in a specific
region of the mouse brain have a built-in mechanism that allows the
cells to participate in the repair and remodeling of damaged tissue
in the region.

As the cells are also present in the human brain, the same capacity
or potential may exist in humans, the researchers say. If they do, it
is possible that the cells' behavior could be enhanced to treat
tissues damaged throughout the brain by disorders such as stroke and
traumatic injury.

The study, reported in the December 15 issue of Cell, was led by Chay
T. Kuo, MD, PhD, a UCSF postdoctoral fellow in the laboratory of
senior investigator Yuh-Nung Jan, PhD.

Kuo is one of 16 UCSF CIRM Stem Cell Scholars – up and coming young
scientists funded by the California Institute for Regeneration
Medicine, established by California voters in 2004 to allocate $3
billion over 10 years to support stem cell research.

"The results were very surprising," says Kuo. "Our results show that
neural stem cells in mice have the ability to sense damage in their
environment that leads to their subsequent proliferation to help
restore local tissue integrity. If we can figure out how this
happens, and determine that it occurs in human neural stem cells, we
may be able to increase the effect and harness it for therapeutic
use."

Understanding this proliferative capacity during environmental change
is critical, he says, as adult neural stem cells in this region may
sometimes proliferate out of control to form brain tumors. This
possibility has been reported and is being explored by scientists in
the UCSF Institute for Regeneration Medicine and UCSF Department of
Neurological Surgery.

The scientists focused their study on postnatal neural stem cells
that lie next to the lining of the brain's lateral ventricles, or
cavity, in a region known as the subventricular zone (SVZ). In 1999,
the lab of study co-author Arturo Alvarez-Buylla, PhD, UCSF Heather
and Melanie Muss Professor of Neurological Surgery, discovered that
cells in this region known as astrocytes function as adult neural
stem cells in mice (Cell, June 11, 1999) and later discovered similar
cells within the human brain (Nature, Feb. 19, 2004). The cells are
recognized as a major source of adult stem cells in the mammalian
brain.

Scientists have known that neural stem cells play a key role in both
embryonic and postnatal mice, driving the development of specialized
cells within the brain such as neurons, astrocytes, oligodendrocytes,
and ependymal cells. And they have identified many of the molecular
pathways that control neural stem cell behavior in embryonic mice.

But relatively little was known about the molecular programs that
control neural stem cells in the postnatal mouse, or how neural stem
cells may respond to tissue damage -- two key questions for
scientists exploring the potential of these cells to treat disease.

To shed light on these issues, Kuo and his colleagues genetically
engineered neural stem cells and ependymal cells in the SVZ of
newborn mice in such a way that they lacked two key proteins, named
Numb and Numblike.

These proteins are known to play a critical role in maintaining
neural stem cell function in embryonic mice, but scientists have not
known their actual function. They suspected that the proteins might
be active in the SVZ of postnatal mice as well. If so, they reasoned,
preventing the proteins' synthesis might inhibit the cells' local
activity and, in so doing, reveal their postnatal function. At the
same time, if the cells' activity was inhibited by the absence of the
proteins, there could be tissue damage in the SVZ, providing a model
for exploring the way in which the neural stem cells responded to it.

The strategy paid off.

Kuo and his colleagues' examination of postnatal mouse brains on
autopsy seven and 14 days after the genetic modification revealed
that absence of proteins Numb and Numblike led to severe brain
ventricle enlargement. This defect resulted from damage of ependymal
cells, which form the epithelial lining of the brain ventricles, and
of neuroblasts, which evolve into neurons. Thus, it was evident that,
as in embryonic mice, the proteins play a crucial role in the
maintenance of cells in the region, and revealed a previously unknown
function for them in assuring ependymal layer integrity.

Wholly unexpected, however, was the fact that damage to the left
ventricular wall was substantially repaired when these sick mice were
examined six weeks later. As a result of a known limitation of the
genetic engineering technique that Kuo employed – some neural stem
cells escaped gene deletion, thus allowing the Numb protein they
synthesized to remain intact – some neural stem cells had continued
to function. Faced with damage in the region, these cells had
responded, mediating the rebuilding of ventricular wall lining and
establishing a modified neural stem cell environment.

The scientists do not know the precise mechanisms by which the stem
cells carried out their response. But it was astonishing, says study
senior investigator Jan, who is , a Howard Hughes Medical Institute
investigator, the Jack and DeLoris Lange Endowed Chair in Molecular
Physiology and professor of physiology and biochemistry at UCSF.

"The holes that had formed in the brain ventricular wall had largely
been repaired. These adolescent mice looked quite good. The finding
shows that the brain has the ability to repair itself and that it is
more plastic than previously appreciated."

The model Kuo devised, says Jan, will provide a powerful tool for
studying the response of neural stem cells of the SVZ to damage
caused by such conditions as stroke and trauma.

It can also be used to test the impact of deleting various genes from
neural stem cells of the SVZ. The results, he says, would contribute
to scientists' understanding of the full pathway of genes needed to
prompt differentiation of neural stem cells both in the brain and in
the culture dish. In this sense, he says, "the deletion of Numb and
Numblike was a test case."

In collaboration with other UCSF neuroscientists, as well as
neurosurgeons, Kuo is currently exploring whether neural stem cells
of the SVZ can respond to damage outside the ventricle region and, if
so, whether inflammation in the traumatized area prevents the stem
cells from restoring the tissue.

And he wonders whether the epilepsy that can occur in stroke and
trauma patients, often years after the injury, results from
unsuccessful attempts by the progeny of neural stem cells to make
synaptic connections with other cells in the damaged region.

Numerous other UCSF labs are also investigating neural stem cells in
the SVZ of the embryonic and postnatal brain, with an eye toward
developing therapies for Parkinson's, epilepsy and ALS, says Arnold
Kriegstein, MD, PhD, the John G. Bowes Endowed Chair in Stem Cell and
Tissue Biology and director of the UCSF Institute for Regeneration
Medicine.

And like the neural stem cells they study, these scientists are
collaborating, making connections aimed at building new material. "As
such," says Kriegstein, "their work demonstrates the power of
synergy."

###
Other co-authors of the study were Zaman Mirzadeh and Denan Wang of
UCSF, Mario Soriano-Navarro and Jose Garcia-Verdugo of Unidad
Asociada Centro de Investigatcion Princepe Felipe-Universidad de
Valencia, Mladen Rasin and Nenad Sestan of Yale University School of
Medicine, and Jie Shen of Harvard Medical School.

UCSF is a leading university that advances health worldwide by
conducting advanced biomedical research, educating graduate students
in the life sciences and health professions, and providing complex
patient care.

Related links:

http://pub.ucsf.edu/newsservices/releases/200402176
UCSF finding advances insight into adult stem cells in human brain

http://pub.ucsf.edu/newsservices/releases/200604108/
UCSF receives CIRM stem cell training grant

http://stemcellfacts.ucsf.edu/
UCSF Institute for Regeneration Medicine

Public release date: 14-Dec-2006
Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco

__._,_.___
____________________________________________
«¤»¥«¤»§«¤»¥«¤»§«¤»¥«¤»«¤»¥«¤»§«¤»¥«¤»§«¤»¥«
¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯
StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
____________________________________________
«¤»¥«¤»§«¤»¥«¤»§«¤»¥«¤»«¤»¥«¤»§«¤»¥«¤»§«¤»¥«
¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯
Recent Activity
Visit Your Group
Yahoo! News

Odd News

You won't believe

it, but it's true

Yahoo! Finance

It's Now Personal

Guides, news,

advice & more.

Yahoo! Groups

Going Green

Share your passion

for the planet.

.

__,_._,___

No comments:



about stem cell research
adult stem cell
adult stem cell research
adult stem cells
against stem cell
against stem cell research
anti stem cell
anti stem cell research
autologous stem cell
autologous stem cell transplant
benefits of stem cell research
blood stem cells
bone marrow stem cells
bush stem cell
california stem cell
cancer stem cell
cancer stem cells
cell stem cell
cons of stem cell research
cord blood stem cell
cord blood stem cells
cord stem cells
diabetes stem cell
embryonic stem cell
embryonic stem cell research
embryonic stem cells
for stem cell research
funding for stem cell research
harvard stem cell
harvard stem cell institute
hematopoietic stem cell
hematopoietic stem cells
history of stem cell research
human embryonic stem cell
human embryonic stem cell research
human embryonic stem cells
international stem cell
mesenchymal stem cell
mesenchymal stem cells
neural stem cell
neural stem cells
nih stem cell
pluripotent stem cells
pro stem cell
pro stem cell research
pros and cons of stem cell
pros and cons of stem cell research
stem cell
stem cell bank
stem cell bill
stem cell biology
stem cell companies
stem cell conference
stem cell controversy
stem cell cures
stem cell debate
stem cell differentiation
stem cell ethics
stem cell funding
stem cell heart
stem cell information
stem cell institute
stem cell line
stem cell lines
stem cell news
stem cell policy
stem cell reasearch
stem cell reaserch
stem cell reseach
stem cell research
stem cell research articles
stem cell research bill
stem cell research controversy
stem cell research debate
stem cell research enhancement act
stem cell research ethics
stem cell research facts
stem cell research funding
stem cell research pros
stem cell research pros and cons
stem cell reserach
stem cell reserch
stem cell technologies
stem cell technology
stem cell therapy
stem cell transplant
stem cell transplantation
stem cell transplants
stem cell treatment
stem cell treatments
stem cell veto
stem cells
stem cells research
support stem cell research
types of stem cells
umbilical cord stem cells
what are stem cells
what is a stem cell
what is stem cell
what is stem cell research