Key Advance In Treating Spinal Cord Injuries

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Key Advance In Treating Spinal Cord Injuries

19 Sep 2008

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

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 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 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.

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Article adapted by Medical News Today from original press release.

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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.