September 20, 2005
Human Neural Stem Cells Partially Cure Mouse Paralysis

UC Irvine researchers used human neural stem cells to partially restore movement ability in mice with spinal cord injuries.

Researchers at the UC Irvine Reeve-Irvine Research Center have used adult human neural stem cells to successfully regenerate damaged spinal cord tissue and improve mobility in mice.

The findings point to the promise of using this type of cells for possible therapies to help humans who have spinal cord injuries. Study results appear online in the Proceedings of the National Academy of Sciences Early Edition.

In their study, Brian Cummings, Aileen Anderson and colleagues injected adult human neural stem cells into mice with limited mobility due to spinal cord injuries. These transplanted stem cells differentiated into new oligodendrocyte cells that restored myelin around damaged mouse axons. Additionally, transplanted cells differentiated into new neurons that formed synaptic connections with mouse neurons.

The ability to grow new myelin sheath would also be very beneficial to patients suffering from multiple sclerosis.

Myelin is the biological insulation for nerve fibers that is critical for maintenance of electrical conduction in the central nervous system. When myelin is stripped away through disease or injury, sensory and motor deficiencies result and, in some cases, paralysis can occur. Previous Reeve-Irvine research has shown that transplantation of oligodendrocyte precursors derived from human embryonic stem cells restores mobility in rats.

“We set out to find whether these cells would be able to respond to the injury in an appropriate and beneficial way on their own,” Cummings said. “We were excited to find that the cells responded to the damage by making appropriate new cells that could assist in repair. This study supports the possibility that formation of new myelin and new neurons may contribute to recovery.”

Coordinated walking ability was restored.

Mice that received human neural stem cells nine days after spinal cord injury showed improvements in walking ability compared to mice that received either no cells or a control transplant of human fibroblast cells (which cannot differentiate into nervous system cells). Further experiments showed behavioral improvements after either moderate or more severe injuries, with the treated mice being able to step using the hind paws and coordinate stepping between paws whereas control mice were uncoordinated.

The cells survived and improved walking ability for at least four months after transplantation. Sixteen weeks after transplantation, the engrafted human cells were killed using diphtheria toxin (which is only toxic to the human cells, not the mouse). This procedure abolished the improvements in walking, suggesting that the human neural stem cells were the vital catalysts for the maintained mobility.

The lack of need to condition the stem cells to become specific types of cells makes this a simpler approach to apply than attempts which used less differentiated human embryonic stem cells.

This study differs from previous work using human embryonic stem cells in spinal cord injury because the human neural stem cells were not coaxed into becoming specific cell types before transplantation.

If human cells can improve movement in mice the likelihood that these same cells would deliver a similar benefit in humans with spinal cord injuries seems high.

The British newspaper The Guardian reports that the stem cells came from neural tissue of aborted fetuses.

Neuroscientist Aileen Anderson and her team at the Reeve-Irvine Research Centre at the University of California, Irvine, used stem cells taken from the neural tissue of aborted foetuses. When injected into the body, they can develop into any type of nervous tissue.

Can anyone confirm this? Neither the UC Irvine press release or the press release of the company that supplied the stem cells (see below) make any mention of this fact.

The company that supplied the stem cells to the UC Irvine researchers is Palo Alto California based StemCells Inc. The StemCells Inc. press release mentions that the Christopher Reeve Foundation was one of the sources of funds for this research (bringing to mind that South Park episode where Reeve's character ate fetal brains and became extremely vigorous as a result)

PALO ALTO, Calif., (September 19, 2005) – StemCells, Inc. (Nasdaq: STEM) today announced results of a published study that demonstrates that the Company’s proprietary human neural stem cells restore the lost motor function of mice with spinal cord injuries. This study is also the first to show the causal relationship between transplanted human neural stem cells and long-term recovery of motor function: The human neural cells were subsequently ablated in some of the mice, and their improved motor function was lost.

The study was conducted by Drs. Aileen Anderson, Brian Cummings and their colleagues from the Reeve Irvine Research Center at the University of California, Irvine. It will be published today online in the Early Edition of the Proceedings of the National Academy of Sciences of the United States of America (PNAS), and will appear in the September 27, 2005 print issue. The study was funded in part by a Small Business Innovative Research Grant from the National Institute of Health (NIH) to StemCells, Inc. Support was also provided by the Christopher Reeve Foundation through its International Research Consortium on Spinal Cord Injury.

The CEO of StemCells Inc. says these are still early days. But what obstacle exists for trying out these stem cells in paralyzed humans right now?

“While we are early in our quest to find a stem cell therapy for spinal cord injury, the design of this study raises the bar for evaluating experimental cell-based therapies in this extremely debilitating medical condition,” said Martin McGlynn, President and Chief Executive Officer of StemCells. “The study clearly demonstrates that our proprietary human neural stem cells make functional new neural cells, and are responsible for the restoration of hind limb function in this animal model of spinal cord injury.”

In the StemCells Inc. press release they refer to the cells as having been isolated from "normal brain tissue".

StemCells, Inc. is a development stage biotechnology company focused on the discovery, development and commercialization of stem cell-based therapies to treat diseases of the nervous system, liver and pancreas. The Company’s stem cell programs seek to repair or repopulate neural or other tissue that has been damaged or lost as a result of disease or injury. StemCells is the first company to directly identify and isolate human neural stem cells from normal brain tissue. These stem cells are expandable into cell banks for therapeutic use, which demonstrates the feasibility of using normal, non-genetically modified cells as cell-based therapies. StemCells is the only publicly traded company solely focused on stem cell research and development and has more than 40 U.S. and 100 non-U.S. patents, as well as 100 patent applications pending worldwide.

On one hand abortion is already legal in the United States and has been for decades. So use of neural stem cell tissue from aborted fetuses does not result in more fetuses getting killed. On the other hand, abortion opponents will surely get angry at the idea of remains of aborted fetuses getting used to develop medical treatments.

Put aside the ethical considerations. Think about the medical implications. The scientific lesson here is that types of neural stem cells already exist that can at least partially and substantially repair spinal cord injury. The delivery of those cells does not require creation of a futuristic high tech artificial biochemical environment in the spine (say complex chemical gradients varying through time) or an elaborate system for controlling the migration and differentiation of the cells. Given the development of the right sort of neural stem cells a substantial amount of spinal repair becomes possible pretty easily.

The technical point here, even for abortion opponents, is that if a way to make the right sorts of neural stem cells can be found then stem cells can fix damaged spines. Granted, some people would prefer a different way to make these stem cells. I expect other ways will be found. But once stem cells can get programmed to the right epigenetic state then the cells will repair spinal cords. That's good news.

The full article (PDF format) is open access and you can start with the abstract.

Update: Be sure to read the comments on this post. Garson Poole points to the use of premature births that die as a source of cells. This neatly sidesteps opposition to abortion. The use of organs from people who unexpectedly die is morally accepted across the political spectrum (with the exception of perhaps a couple of religious demoninations that do not oppose this choice by others). So why not the same with premature births?

Share |      Randall Parker, 2005 September 20 12:05 PM  Biotech Stem Cells


Comments
Marvin said at September 20, 2005 4:50 PM:

Research in the US will probably be limited to animal experiments, using either human or animal stem cells. In South Korea they plan to do the same basic procedure in humans, using human stem cells. US ethics committees are probably not very close to approving this type of research in humans. If the results in South Korea are good, everything will change. Anti-abortion people won't be able to stop this once people clearly start to benefit medically.

Garson Poole said at September 20, 2005 8:32 PM:

Human fetal cells were used previously in rat experiments as described in a news article at the Betterhumans website entitled "Human Nerve Stem Cells Regenerate Rat Brain". Here is a link and an excerpt:

In the current study, human cells called neurospheres were derived from fetuses and transplanted into rats with a model of stroke. Neurospheres are clusters of cells that, under certain conditions, differentiate into such brain cells as astrocytes, oligodendrocytes and neurons.

Four weeks after transplantation, the researchers examined the cells' ability to survive, migrate and differentiate into the brain, and found robust survival of human cells transplanted into tissue near stroke-damaged brain regions. Further, nearly half of the transplanted cells that migrated toward the damaged areas were neurons, indicating that the transplanted cells could develop into appropriate cell types.

There is also ongoing research using fetal/infant liver cells as described in a news article in "Nature Medicine" entitled "Research with premature infant livers touches a nerve". Here is a link to the article but it is only available to subscribers now, and here is an excerpt.

Reid, a researcher at the University of North Carolina, is trying to isolate stem cells from the livers of premature infants who have died. The university was wary about her proposal, but after five years of meetings and reviews, in 2002, it granted her permission to proceed.

Reid's program is the first of its kind in the US. Premature babies are generally too small and underdeveloped to qualify as either donors or recipients of organs. Not surprisingly, Reid and her colleagues have found that the project is fraught with challenges and ethical dilemmas. In some cases, families must be approached for the organs only hours after the mother has given birth and many devastated parents decline. The researchers enlisted the help of a local agency that asks families for adult organs.

During the past two years, Reid has collected about 12 neonate livers and says her team has been able to harvest cells from the livers seven to eight hours after death. She says the organs are thick with hepatic progenitor cells and the cells grow more rapidly than those harvested from adult livers.

This research area will be very controversial. Yet, there may not be major opposition to the use of tissue from infants that die of "natural causes" after birth.

Randall Parker said at September 20, 2005 8:44 PM:

Garson,

Highly excellent search work. Much appreciated.

On the use of premature birth dead babies: Wow! This is akin to using organs from adults who die. It is routine. Encouraged across the political spectrum. Everyone accepts that. This could work. Opens up a lot of possibilities!

Patrick said at September 21, 2005 4:09 AM:

I agree, use of stem cells from natural deaths is objection free, at least from any mainstream religious perspective.

There is still that "ick factor", but I suspect that the number of voters who will go "ick" at a cure for spinal damage is a small and ignored minority.

I'm fully sympathetic with the ethical permission issues. At my last job we were trying to do medical experiments (not harmful, actually helpful) on 7 year olds and it took a year to arrange permission, we had to jump through so many hoops it was just about impossible.

Which is exactly why my employer chose to not make products for younger children (ie below 7). It was just too hard to do any testing. So the children remain untreated, and the ethics board is happy.

Bitter? No...

ziel said at September 22, 2005 5:47 PM:

Since these are stem cells from fetuses, I take it that they qualify as "adult" stem cells rather than "embryonic" stem cells?

Randall Parker said at September 22, 2005 6:46 PM:

Ziel,

Those stem cells from fetuses are probably less differentiated than stem cells you'd get from adult humans or even from children. So while the are not pluripotent (at least not with today's technology) they are probably rather more flexible than adult stem cells that come from actual adults. Though I'm speculating.

Post a comment
Comments:
Name (not anon or anonymous):
Email Address:
URL:
Remember info?

                       
Go Read More Posts On FuturePundit
Site Traffic Info
The contents of this site are copyright ©