Episode Transcript
Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.
Interviewer: After receiving stem cell therapy, mice with a multiple sclerosis-like condition go from being nearly paralyzed to walking. My guest and co-lead author of this study, Dr. Tom Lane, talks about these exciting results just published in the Journal of Stem Cell Reports. Dr. Lane, what is multiple sclerosis?
Dr. Lane: Well, MS is an autoimmune disease and essentially it's a misguided attack of the immune system against proteins within the central nervous system, proteins that are primarily enriched within the myelin sheath. And so this is why many people that have MS have impaired motor skills or problems with vision as well as a variety of other clinical problems.
Interviewer: Can you explain what myelin is?
Dr. Lane: Myelin, a simplest explanation is it's analogous to the rubber sheath that encircles an electrical wire. And so the myelin does a very similar thing. Myelin wraps around axons. The axons extend from the nerve cell body and similar to an electrical wire, impulses are sent down the axon to allow us to do what we're doing right now-talk, move. And so the myelin sheath is necessary for this to occur.
Now, if that myelin sheath is damaged or destroyed in any way, that disrupts the conduction of the nerve impulses. So the primary area of research right now in my laboratory is focused upon trying to repair the damaged myelin.
Interviewer: And so you look at this problem in mouse models. Why did you choose that way to research the problem?
Dr. Lane: Well, the mouse recapitulates many of the clinical and histological features that we see in MS patients, inflammation of the central nervous system and demyelination. They have some impaired motor skills. A very small percentage of animals will be completely paralyzed, but we provide the necessary food and water for them because ultimately they would not be able to do so, because animals will have to stand on their hind legs to acquire the food.
Interviewer: Oh, right. So you injected them with neural stem cells. Correct? What were the main findings in your study?
Dr. Lane: Well, it was kind of surprising. Science works in funny ways and this was a happy accident for lack of a better word. We had started these experiments using human neural stem cells, and these were provided by my collaborator and good friend, Dr. Jeanne Loring, who is the Director of the stem cell center at the Scripps Research Institute in La Jolla. And within the central nervous system, rejection of foreign tissue has been somewhat controversial whether they would be recognized as foreign or not. So that was the original idea behind doing these experiments.
And so we surgically engrafted these human neural stem cells into the spinal cords of animals and my post doctoral fellow, Dr. Lou Chen, who is first author on this particular paper, came to me and said the mice that we transplanted are walking. And I didn't believe her. And it's not that I didn't believe her, but I was surprised.
So we went down and I looked at the animals. And sure enough, the control animals had what I would have expected, severe paralysis, whereas the animals that we had transplanted with the human neural stem cells within a remarkably short period of time, about 10 to 14 days, had regained motor skills.
Interviewer: Wow!
Dr. Lane: Yeah, and the important point is that these animals exhibited this improved walking up to six months post-transplant which was in my opinion remarkable.
Interviewer: What was the reaction in the lab when you found these mice that were able to walk again?
Dr. Lane: Surprise, excitement, skepticism.
Interviewer: Oh, yeah?
Dr. Lane: A lot of skepticism and primarily spearheaded by myself because we had to repeat the experiment. And of course, we did it a number of times and importantly, we had other people generate the human neural stem cells to make sure it wasn't something unique to our laboratory, the way we're doing it. So we acquired neural stem cells from different sources that were generated in the same way and we saw the same therapeutic recovery, so we were very relieved by that. And then finally we realized this was something real and so we started interrogating the underlying mechanisms.
Interviewer: So what do you think is happening?
Dr. Lane: Well, it's a great question and so we're just gradually peeling the layers off. And what we know and what's presented in this report is one of the other very surprising findings was that about eight days following transplantation of these human neural stem cells, they're gone; they're rejected. But the clinical recovery as, I indicated, lasts out to at least six months post transplant. That's at least as far as we looked.
And what we know is that these transplanted human neural stem cells, in a very short period of time, on a very immunomodulatory. And so in other words, they can change potentially bad T cells, that is T cells that are reactive to myelin into good T cells that are called regulatory T cells. Now these regulatory T cells, what they do is they secrete molecules that dampen inflammation. So that's one mechanism by which we believe these cells are promoting therapeutic recovery and histologic recovery in these animals.
The other avenue, which we're still actively pursuing, is what is being secreted by these cells that allow for remyelination to occur?
Interviewer: Okay. So the stem cells themselves aren't the ones that are doing the repair. They're promoting other cells that are in the mouse already to do that repair job.
Dr. Lane: That is exactly correct.
Interviewer: Okay, interesting.
Dr. Lane: And I think the clinical take away, at least from this preliminary observation or these findings, is the fact that the cells are no longer there suggests several things to me at least. One, you don't need stem cells from a patient to inject to get a therapeutic long-term recovery. And along these veins you don't stem cells to be present for the entire time for long-term recovery to occur. And then finally we can identify what factors are being secreted from these cells and potentially make these "drugable."
Interviewer: Okay.
Dr. Lane: And that way, rather than having to engraft stem cells into a patient, which can be challenging from a medical standpoint, we can develop a drug or drugs that could be used to deliver it much easier.
Interviewer: There are many drug therapies available for multiple sclerosis patients, but do any of these therapies address the myelin problem?
Dr. Lane: That's a great question. The drugs that are available, the main three are called the ABCs: Avonex, Betaseron, and Copaxone. What those drugs are designed to do are to stop the infiltration of myelin reactive lymphocytes into the central nervous system. So, in other words, to stop the progression of the disease. None of these drugs as we know them function to restore or promote remyelination.
So MS, once you're diagnosed with it, about 85% of people that have the initial form of the disease have the relapsing, remitting form of the disease. Ultimately though they will progress into what's known as the progressive form of the disease. And the progressive form of the disease, there are no FDA approved therapies that are available to MS patients.
Interviewer: Okay. And so is that where you're taking the research now?
Dr. Lane: Yes, but we report in this paper is that our human neural stem cells secrete TGF-beta 1 and 2, that's transforming growth factor beta 1 and 2.
Interviewer: That's a molecule.
Dr. Lane: That's a molecule. That's exactly right. What's interesting is we can take TGF-beta 1 and 2 in vitro using our particular cells that we draw from our animal models of MS, and they function the same way. They convert bad T cells to these regulatory T cells. So we're very excited by this. But I think inevitably there have to be other molecules involved, so we have to just take it one day at a time and slowly work through the problem.
Interviewer: Do you see that this work might lead to clinical trials at any point?
Dr. Lane: I hope so. That's the goal of most people doing translational type of therapy and it's one of the reasons I wanted to come to the 人妻中出视频 of Utah, because they have such an outstanding record of this. So that's where we're moving. We want to try to move as quickly and carefully as possible. The emphasis being on carefully to make sure we have something safe. I would love to have something that could promote repair and ease the burden that patients with MS have, and hopefully see some type of therapeutic recovery.
Announcer: Interesting, informative, and all in the name of better health. This is the Scope 人妻中出视频 Sciences Radio.