Japan Heals Paralyzed Monkeys Using Non-Embryonic Human Stem Cells

Paralyzed marmoset healed with stem cells
Japanese scientists healed spinal injuries in marmosets. They jumped for joy in only six weeks.

In the debate over stem cell research, it’s not just about what you can do, it’s how you can do it. Scientists in Japan recently announced that they had successfully treated small paralyzed monkeys (marmosets) for spinal cord injury. Each marmoset was injected with human stem cells nine days after spinal damage left them paralyzed from the neck down. In only three weeks the marmosets regained control over their limbs, and in about six weeks they were jumping around again! This sort of miraculous healing is becoming more common with stem cell treatments, but the Japanese team at Keio University may have exceeded certain expectations. That’s because instead of using embryonic stem cells, the researchers took human skin cells and modified them with four different types of genes to turn them into induced pluripotent stem cells (iPS). These cells were then injected into the marmosets to treat their injury. With iPS cells there are no concerns over the destruction of human embryos. While this work with marmosets is far from the most advanced stem spinal cord treatment we’ve seen, it is promising research. With multiple avenues towards creating treatments, it looks more and more likely that we’ll have a spinal cord injury therapy available to us in the years ahead.

The treatment of spinal cord injury has already advanced beyond work in monkeys. Geron officially began their clinical trials using embryonic stem cells weeks ago with their first human patient. Considering the impressive work originally done by Hans Keirstead using rodents and embryonic stem cells, the Geron trial seems very promising, though it will be years before it could possibly become a widely available therapy.

Work done by Keio University and the Central Institute for Experimental Animals is even further behind, but it holds a particularly compelling advantage: the avoidance of embryonic stem cells. With genetic therapies, scientists led by Hideyuki Okano were able to induce pluripotency in regular human skin cells. Those cells then differentiated into nerve cells and partially healed the damage in the injured marmosets. According to the AFP, forehand gripping strength eventually recovered to around 80%. The iPS cells were watched to see if they would develop into tumors, a common worry when working with stem cells. Fortunately, after three months, no such tumors were detected in the marmosets. Okano presented this work to the Molecular Biology Society of Japan on December 7th.

By not relying on human embryonic stem cells (hESC), Okano and his team sidestep a contentious debate over the use of destroyed embryos. hESC, and its association with abortion and other reproductive issues, was one of the most discussed topics in the US debate over stem cell research. George W. Bush’s ban on some forms of stem cell research can almost be certainly traced back to the public perception of hESC. While views on the use of hESC differ around the world, induced pluripotent stem cells are a means of avoiding even the potential for controversy. US and Japanese teams have been transforming skin cells into iPS cells since 2007, with success for differentiation into a variety of cell types, including blood.

Yet the use of iPS is far more important than its ability to quell controversy. Geron’s approach to treating spinal cord injury is a good one, but it relies on a specific cell type (embryonic stem cells). If, in the future, scientists find that hESC has a particular drawback (links to cancer, problems with acceptance by the recipient, or whatever you care to imagine) then stem cell based spinal cord injury therapy could be in jeopardy. Luckily, the work at Keio University relies on an entirely different kind of cell (iPS from skin). If hESC fails, iPS could still succeed. If iPS fails, hESC could still succeed. As long as we have a diversity of approaches we have a better chance for long term viability of spinal cord treatments. Considering that the development of new drugs and medical therapies is often tumultuous, the chance of at least one of these approaches being stalled in the future is very likely. It’s good to have backup.

There is room then, for both iPS and hESC in the pursuit of a spinal cord injury treatment. However, neither of these approaches looks like it will be an immediate aid to those people who already suffer from paralysis. The Geron clinical trial is treating patients within 14 days of the injury. Okano and his team injected marmosets nine days after damaging their spinal cords (according to the AFP this is the “most effective timing” for treatment). Therapy for paralysis, at least now in this early stage, seems to be more of a response to new injury, rather than as a method for healing an old one. That’s still amazing, don’t get me wrong, but it may take a very long time before we can use similar techniques to treat injuries that are years or decades old. Sadly, paraplegics and quadriplegics around the world will need more patience.

Even for those who are injured in the future, iPS cells, may have a drawback compared to hESC. It can take six months for treated human skin cells to become pluripotent and ready for injection into recipients. That means that in the time it takes to create iPS cells from scratch the window for successful spinal cord treatment would close. Okano and his colleagues are working with the Osaka National Hospital to design an “iPS cell bank” where donors could store iPS cells in case of future injury. It’s unclear if hESC would require similar banking (though without you donating to yourself, of course) in order to make them practically available to patients as needed.

The path to stem cell based therapy for spinal cord injury is not a clear one. Still, I believe the work done by Okano and his colleagues is a valuable step in that journey. We need multiple approaches to ensure success and to find the best possible treatment. Hopefully, with multiple teams working on this problem from multiple angles we will arrive at a solution in the near future. The promise of stem cell technology is extraordinary. Fulfilling that potential may take years, but I have no doubt it will be well worth the efffort.

[image credits: © Raimond Spekking / Wikimedia Commons / CC-BY-SA-3.0 & GFDL (modified)]
[sources: AFP, Mainichi Daily News]

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