Key Advance In Treating Spinal Cord Injuries

http://www.medicalnewstoday.com/articles/122160.php

Main Category: Neurology / Neuroscience
Also Included In: Stem Cell Research;  Pain / Anesthetics
Article Date: 19 Sep 2008 - 7:00 PDT

Researchers in Rochester, N.Y., and Colorado have 
shown that manipulating stem cells prior to 
transplantation may hold the key to overcoming a 
critical obstacle to using stem cell technology 
to repair spinal cord injuries.

Research from a team of scientists from the 
University of Rochester Medical Center and the 
University of Colorado Denver School of Medicine, 
published today in the online Journal of Biology, 
may lead to improved spinal cord repair methods 
that pave the way for victims of paralysis to 
recover the use of their bodies without the risk 
of transplant-induced pain syndromes.

The research focuses on a major support cell in 
the central nervous system called astrocytes. 
When nerve fibers are injured in the spinal cord, 
the severed ends of the nerve fibers fail to 
regenerate and reconnect with the nervous system 
circuitry beyond the site of the injury. During 
early development, astrocytes are highly 
supportive of nerve fiber growth, and scientists 
believe that if properly directed, these cells 
could play a key role in regenerating damaged nerves in the spinal cord.

The Rochester team - which consists of biomedical 
geneticists Chris Proschel, Ph.D., Margot 
Mayer-Proschel, Ph.D., and Mark Noble, Ph.D. - 
are pioneers in manipulating stem cells to 
generate nervous system cells that can be used 
for therapeutic treatments. Rather than 
transplanting naïve stem cells, the team has 
adopted an approach of pre-differentiating stem 
cells into better defined populations of brain 
cells. These are then selected for their ability 
to promote recovery. Here glial restricted 
precursor (GRP) cells - a population of stem 
cells that can give rise to several different 
types of brain cell - were induced to make two 
different astrocyte sub-types using different 
growth factors that promote cell formation during 
normal development. Although these astrocytes are 
made from the same stem cell population, they 
apparently have very distinct characteristics and functions

"These studies are particularly exciting in 
addressing two of the most significant challenges 
to the field of stem cell medicine - defining the 
optimal cell for repair and identifying means by 
which inadequately characterized stem cell 
approaches may actually cause harm," said Noble, 
who is also co-director of the New State Center 
of Research Excellence in Spinal Cord Injury, one 
of the primary funders of the research.

The research team in Colorado, which consisted of 
Stephen Davies, Ph.D. and Jeannette Davies, 
Ph.D., transplanted the two types of astrocytes 
into the injured spinal cords of rats and found 
dramatically different outcomes. One type of 
astrocyte was remarkably effective at promoting 
nerve regeneration and functional recovery, with 
transplanted animals showing very high levels of 
new cell growth and survival, as well as recovery 
of limb function. However, the other type of 
astrocyte not only failed to promote nerve fiber 
regeneration or functional recovery but also 
caused neuropathic pain, a severe side effect 
that was not seen in rats treated with the 
beneficial astrocytes. Moreover, transplantation 
of the precursor cells themselves, without first 
turning them into astrocytes, also caused pain 
syndromes without promoting regeneration.

"To our knowledge, this is the first time that 
two distinct sub-types of astrocytic support 
cells generated from a common stem cell-like 
precursor have been shown to have robustly 
different effects when transplanted into the 
injured adult nervous system," said Mayer-Proschel.

"It has long been a concern that therapies that 
promote growth of nerve fibers in the injured 
spinal cord would also cause sprouting in pain 
circuits," said Stephen Davies. "However by using 
the right astrocytes to repair spinal cord 
injuries we can have all the gains without the 
pain, while these other cell types appear to 
provide the opposite - pain but no gain."

"These results emphasize the importance of 
astrocytes in controlling the outcome of 
neurological disease processes," said Proschel. 
"In addition, because transplants of 
undifferentiated stem cells harbor the risk of 
making deleterious astrocytes, it is important to 
understand their properties and how they might 
form. By being able to study different types of 
astrocytes derived from a common neural 
precursor, we are now underway to finding means 
of preventing the formation of the deleterious 
astrocyte type in the first place."

The research teams in Denver and Rochester 
consider the dramatically dissimilar outcomes 
between the different astrocyte transplants a 
development that can change the way stem cell 
technologies are used to repair spinal cord 
injuries. To that end, the researchers are in the 
process of developing a safe, efficient and 
cost-effective way to use this approach to better 
define the optimal human astrocytes with an eye 
toward use for clinical trials.

----------------------------
Article adapted by Medical News Today from original press release.
----------------------------

Also participating in this research was Ningzhe 
Zhang, Ph.D., with the University of Rochester 
Department of Biomedical Genetics. In addition to 
the New York State Spinal Injury Research Board, 
this research was supported by the Lone Star 
Foundation and donations from private individuals.

Source: Mark Michaud
<http://www.urmc.rochester.edu/>University of Rochester Medical Center

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