IRA FLATOW, host:
Some stem cell research news from this side of the pond. Scientists from the University of California at Irvine developed a treatment derived from human embryonic stem cells to treat rats with spinal cord injuries. And when they gave their treatments to the site of the spinal cord injury within days of the damage, the rats regained some mobility. Research is being reported in The Journal of Neuroscience. What might this mean for humans, especially people with chronic spinal cord injuries? Here to answer that question is Hans Keirstead, an associate professor at the Reeve-Irvine Research Center and co-director of the UCI Stem Cell Research Consortium at the University of California-Irvine.
Welcome to the program.
Professor HANS KEIRSTEAD (Associate Professor, Reeve-Irvine Research Center): Well, thank you. Nice to be here.
FLATOW: You know, I think we got to do a little physiology lesson here in neurology. Give us an idea, in order to understand what you've done, a basic understanding of what happens when the spinal cord is injured, and then we can go on from there.
Prof. KEIRSTEAD: When the spinal cord is injured, you really have a two-step process. Firstly, you've got the initial site of injury, which is so destroyed it just dies, gets resorbed, eventually turns into a cavity. Around that, you have a penumbra of spare tissue that's connecting the spinal cord above and below the injury site. The wires are still there, communicating above and below, but they don't have their insulator on them. They're demyelinated. That insulator is called myelin.
Prof. KEIRSTEAD: And it is lost in spinal cord injury. So that penumbra of tissue that should actually communicate the spinal cord above and below the injury--it's functionally dead, even though it's there.
FLATOW: Now tell us what you did in connection with this in this paper that you've published.
Prof. KEIRSTEAD: What I did was develop a cell population to address that deficit. I think trying to fill in that hole is a pretty big task. So I sought to take a little bit more of a humble approach and just try to deal with the remaining tissue and try to get it functional again so that tissue has lost an insulator called myelin, and myelin is produced by a particular brain cell type. That's called an oligodendrocyte. And what I did was I took human embryonic stem cells, and I coaxed them with growth factors and many other means to become not toenails, not hair, not skin, but only this type of brain cell type that makes this myelin, and we succeeded in generating a very high purity, about 98 percent pure population, of these cells.
FLATOW: Keep going.
Prof. KEIRSTEAD: Well, it's the--that's the first time that a high purity population of anything has been derived from human embryonic stem cells so it shows that we can do it. It shows that we can make a clinically useful high-purity population that can be used to either do basic research for or treat a deficit.
And so what we did is we put them into spinal-cord-injured adult rats, and we modeled this injury such that it reflected the greatest proportion of human injuries, human spinal cord injuries, and we induced injuries in adult rats that modeled human injury and then we waited for seven days. So this was a clinically relevant paradigm. And then we transplanted our human embryonic stem cells that had been predifferentiated to this particular cell type, and then we waited for a couple of months, and see what happened and we got some wonderful results. The transplanted cells did restore the lost myelin. They made that tissue repaired in that they could--the myelin, again, was restored to them, and it had a tremendous effect on the ability of the animals to walk again. They...
FLATOW: Did they walk again?
Prof. KEIRSTEAD: Yeah, the uninjured animals could walk extraordinarily poorly. They couldn't lift their bellies off of the ground all the time. They--sometimes they could, sometimes they couldn't. It was a--it's--they were very, very visually lame. But the animals that were transplanted with these human embryonic stem cell derivatives, within a couple of months' time, they consistently, all the time, were able to lift their bellies off when they walked, so they could support the entirety of their weight, and what was very exciting is that the front paws and the rear paws acted in a coordinated manner again. So that meant that the spinal cord above and below the injury site was actually communicating again.
FLATOW: There was one sort of downside to the experiment in that you had to apply the stem cells at a precise period in the--in therapy, right?
Prof. KEIRSTEAD: We applied them at two different times. We transplanted them at seven days after injury and you get repair, and then we transplanted them at 10 months after injury and you do not get repair. And I had actually expected that result, in that the chronic spinal cord and very old injury is very, very different from an acute injury. We designed this treatment specifically to go after the early injuries, and I really didn't want to publish that data because it would mislead the patient community into thinking that perhaps it could also work for old injuries, so I waited and did the old injury study and published the two together to give a more complete story.
FLATOW: So what is different about the two that it works early but not late?
Prof. KEIRSTEAD: The old injury is scarred, just sort of like you'd expect it to be. It's a similar lesion to a very old multiple sclerosis lesion. The word `sclerosis' means scar. And a spinal cord injury that's very old is actually much like a multiple sclerosis lesion that's old. Both have a component in them that a young injury does not. And that's scar. That scar prevents the cells that I transplant from actually repairing the myelin to those demyelinated or naked axons in the spinal cord.
FLATOW: What advantage did the human embryonic stem cells give you in this case?
Prof. KEIRSTEAD: Human embryonic stem cells are the only cell type we know where we can take one cell, make it into two, into four, into 16, on and on so that we can get a cubic yard of the stuff, and humans are big and there's a lot of us, so we need a lot of tissue. This is the only cell type that we can generate such a tremendous amount of bulk from so that we can eventually pack them all into little tubes with the goal of sending them around to emergency rooms and treating humans that come in with a spinal cord injury.
FLATOW: All right. Let's go to that goal. How close are we to that? Are human trials under way?
Prof. KEIRSTEAD: No, human trials aren't under way yet. The work that we've done is preclinical. So we're actively engaged in preclinical studies of efficacy--Does it work?--and safety--Does it do any harm? And although we haven't seen any instances of harm yet, we have to do some tremendous safety studies, and they're long--in some cases, a year long--to make sure that no harm comes from the transplantation of these human cells, and pending the successful outcome of these safety studies, then, yes, I do expect we'll be going immediately into clinical trials. I wish I could say how long they'll take, but I can't.
FLATOW: So, as you say, before, this is for--this would be for new spinal cord injuries, not ones that are older than a few months?
Prof. KEIRSTEAD: That's right, yeah. Another big area of research here at the Reeve-Irvine Research Center is addressing chronic injury. So we've got active research programs that are specifically designed to treat a chronic injury. Those studies are under way. They're not quite as advanced as these acute treatments, but they're coming.
FLATOW: For your research, you used some of the federally approved human embryonic stem cell lines, right?
Prof. KEIRSTEAD: Yes, I did.
FLATOW: And you also work in the state of California, which has decided to finance its own stem cell initiative. That work will benefit you, too, I imagine.
Prof. KEIRSTEAD: You know, there's a tremendous amount of enthusiasm here. The people of California voted with great majority to fund human embryonic stem cell work and stem cell work in general. The enthusiasm out here is just terrific, and it's--that alone is having tremendous effects, but when the dollars start flowing, that's going to speed research. There's a truth in research that it goes as fast as the dollars flow, and, fortunately, we've got a great base to start basic research and develop therapies from them.
FLATOW: I think there's probably no better way to speed up, you know, or change the ideas about human embryonic stem cells than for something like your research to pan out and prove its use.
Prof. KEIRSTEAD: Well, you know, I have to say that I think this is a good demonstration of the potential of these cells. I have to also say that spinal cord injury is particularly suited for a cellular replacement strategy, the use of these stem cells. Other indications--Parkinson's, Alzheimer's, multiple sclerosis--they can also be addressed, I believe, but the--it's a harder hurdle. It really is. We're getting there, and many, many--as a scientific community, we're working on those other indications, but the systems are a little more complex. In spinal cord injury, we've got a clear deficit. We're addressing it directly and it's particularly suited. We'll see the others come along.
FLATOW: Because you have to remove the scar tissue first before you can try to link it up again.
Prof. KEIRSTEAD: That's right so...
FLATOW: Is there a way of doing that with other kinds of stem cells or other kinds of modality?
Prof. KEIRSTEAD: There's many, many strategies right now being explored to address this scar. It's one of the last great barriers in treating human brain and spinal cord injuries. How do you get rid of that scar? We've got a couple strategies under way here at the Reeve-Irvine, and there's a handful of scientists through the world that are doing other techniques. Let's hope one of them breaks soon.
FLATOW: We're going to be talking a little bit later with scientists from the UK doing stem cell research. They sort of are further ahead of us in human embryonic stem cell research.
Prof. KEIRSTEAD: Well, in every--it depends on what you're talking about. In spinal cord injury, I think that these cells are showing tremendous promise. In other areas, they're showing promise for--in the hands of different investigators. So everybody's moving along at their own paces and...
Prof. KEIRSTEAD: ...all the power to them. Go for it.
FLATOW: And where do you go from here?
Prof. KEIRSTEAD: Well, I am working on these chronic injury treatments and trying to get that scar gone, develop another cell population so we can actually circumvent this scar altogether--leave it there, but work around it--and another strategy for treating acute injuries, and then trying to transpose all this into multiple sclerosises, as well, so I've got my hands full.
FLATOW: You mean it's actually possible to leave the scar there and sort of thread the new wiring through it?
Prof. KEIRSTEAD: It's a possibility, yes, that we're investigating with a great deal of vigor.
FLATOW: All right. We're going to--thank you very much for taking time to talk with us.
Prof. KEIRSTEAD: My pleasure.
FLATOW: Hans Keirstead is associate professor at the Reeve-Irvine Research Center and co-director of the UCI Stem Cell Research Consortium at the University of California at Irvine.
We're going to take a little short break and talk more about--I mentioned before the UK being, you know, ahead in embryonic stem cell research. They have different laws regulating it. We're going to be talking about also some interesting stem cell research that's going on over there, and a little bit later in the program, the science adviser to Tony Blair will be here, Dr. David King. So stay with us. We'll be right back.