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Jeanne Loring: Stem Cells: What We Know and What We Don’t

Jeanne Loring: Stem Cells: What We Know and What We Don’t

Loring: I want to thank Meredith Salisbury for inviting me or causing me to be invited I guess because this isn’t my normal venue. But I think this is a subject that you’ll find really interesting so if I can have your attention for maybe the next eight minutes or so, I think there are a couple of things I can tell you that you didn’t know before.
So this is what most people know about stem cells, they know what they read in the news and there’s one example that happened relatively recently, maybe you’ve heard of it, was when Gordie Howe, who is a legendary hockey star suffered a serious stroke in October of 2014. Almost immediately a company, called Stemedica, in San Diego, they offered to treat Howe for free with stem cells in a so-called clinical trial in Tijuana, Mexico. What happened was that he did get better but stroke victims get better and worse, especially if it’s a very short term after the stroke, but the press just went completely crazy about this and I think the most—“USA Today” of course said that there was a dramatic recovery and Keith Olbermann gave this really gushy interview with one of the Stemedica vice presidents in which he essentially said, “This is a miracle” and Gordie Howe’s doing everything except for dancing the Macarena. So the result of this is people started contacting Stemedica and they were asking for a similar stem cell treatment and the cost to them, rather than the free Gordie Howe treatment was $20,000 to $30,000 dollars.
So what’s wrong with having a miracle like this? First of all, the treatment that Gordie Howe received was not a clinical trial. I mean, it’s simply is not a clinical trial. Clinical trials have to have a certain format because otherwise we don’t learn anything from them. And so you have to show that whatever you’re giving people is safe and ultimately you have to show that it’s effective and you have to follow up with the patients and none of this was done for Gordie Howe nor any of the other patients at this stem cell clinic. Interestingly, and perhaps obviously to scientists at least there’s no evidence at all that the cells that Stemedica gave to Gordie Howe have any effect whatsoever on stroke nor any other disease, but stories like this have fueled a multi-million dollar industry. Stem cell clinics are sort of starting to show up on every street corner and there are more than 100 in the US alone, we can’t really keep track of them, but they’re all offering some kind of a therapy that is desirable to people. And the FDA actually oversees these clinics and medical boards but they don’t have the bandwidth to go to each one of them, they’ve closed a few of them. A couple of people have lost their medical licenses but it is extremely slow and very frustrating and as I said, these new clinics keep jumping up all the time. It’s important to know that these unregulated stem cell treatments can be dangerous. In most cases they’re benign, they don’t do any harm, they don’t do any good, but there have been some cases in which people were harmed quite seriously and there have been some deaths from stem cell therapy, it’s from these unregulated clinics.
Okay, so here’s what—if you just do a Google search of stem cell clinics you’ll find that they claim cures of virtually every disease you can think of and I think this particular fellow who works for, he’s actually a patient, he says there’s no guarantee that a stem cell treatment will work, what he can guarantee is that your wallet will be a lot lighter. So these are the claims of cures and here’s the evidence for cures. There have been absolutely no cures that have been shown medically to occur as a result of one of these stem cell clinics treating patients. I like this cartoon because it illustrates how essentially a business can grow based on—I mean, they can have a drive-thru, a drive-thru Starbucks actually just started in my neighborhood, so why not a drive-thru stem box? Okay, the only stem cell treatment that is now approved by the FDA is the bone marrow transplant. It’s been around since the 1960s. Bone marrow cells are able to give rise to red and white blood cells and people who have leukemia in which they get total body radiation wipes out their own bone marrow can get a bone marrow replacement and this is becoming more and more successful all the time. However, most of the unapproved clinics use stem cells in liposuction. A lot of the people who have started these clinics are plastic surgeons. The cells that you get out of liposuction are in fact stem cells but the only things that they can make are cartilage, bone, or fat. And you can imagine putting these stem cells in the wrong place might result in—in one case we’ve heard about in which a woman went back to her doctor saying that every time she closed her eyes she heard a clicking. So it turned out that this guy had put stem cells into her eyelids and they turned to bone.
So what I want to tell you about is what’s promising in the future and a lot of the promise that we feel is in the future for stem cells are with cells called pluripotent stem cells. They’re two different kinds, two very different kinds of stem cells. And I’m going to tell you a little bit about what the real science is going on right now. These cells, pluripotent of course, you’ve all taken Latin so you know that means many powers, these cells can make every cell type in the body. Pluripotent stem cells are being developed for therapy, they’re also being developed for drug development for drug screening and a lot of other uses. In fact, I can talk about some of the other uses we’re using the cells for after my talk, but not during it. Okay, so two types of stem cells, this is a useful way to remember, adult stem cells can do a couple of things but pluripotent stem cells can do everything. Okay, where do pluripotent stem cells come from? The original human pluripotent stem cells came from discarded embryos after in vitro fertilization clinics, after they were discarded. They exist in the inner cell mass, which is just a tiny little bit of cells within the embryo. These were made into what’s called embryonic stem cells in 1998. The other type of pluripotent stem cell, which has expanded the field greatly start with skin biopsies in volunteers and this was reported for the first time in 2007. From skin biopsies or from blood or from just about any tissue in a person you can generate a culture of cells or you can generate cells which can then be reprogrammed using a transient expression of some transcription factors for those of you who know what that means and they make induced pluripotent stem cells. So that means that we can custom make cells that are pluripotent, that can give rise to every cell type in the body from any one of you or all of you for that matter. It’s important to recognize that pluripotent stem cells exist only in culture dishes, they aren’t things that you get out of a person. And the stem cell parental advice, you can be anything you want when you grow up. Okay, so if you visualize all the cell types that pluripotent stem cells can make, it’s useful to look at them as sort of a tree with a lot of branches. So you see in this case the trunks of pluripotent stem cells and all the branches and leaves that some of the cell types, they can give rise to everything as I said, but some of these cell types are being actually used for right now in clinical trials, some of the cell types that pluripotent stem cells can make. And then others are being used in pre-clinical applications.
I’m going to talk about two of those for Parkinson’s disease and Multiple Sclerosis, these are from my own lab. Okay, so the first, this was an important milestone because the FDA approved a clinical trial just last fall for the use of embryonic stem cell–derived pancreatic islet cells. Okay, now I think most of you know that in type 1 diabetes the immune system attacks the islet cells. The cells that make insulin, they die and people are dependent on injections of insulin for the rest of their lives. So wouldn’t it be cool if you could replace those cells? And that’s what this company called Viacyte in San Diego is working on doing and they’re now, have, I think, transplanted three or four patients. They put the embryonic stem cell–derived islet, pancreatic islet cells, inside this little device, which protects the cells from being rejected. The problem with embryonic stem cells is that they come from a different individual and so they are recognized as being non-self and they’re rejected almost immediately. So they encapsulated these cells in something that they describe as like a tea bag in which the insulin can get out but the immune system can’t get in and kill the cells. Another important stem cell therapy is for macular degeneration, which is a disease of the aged along with a lot of other diseases. This was developed by a company called ACT, which is now called Ocata in Massachusetts and what they did was to make a particular cell type called a retinal pigment cell from embryonic stem cells and then they transplanted these cells into the eyes of people who had macular degeneration. These cells clean up a lot of the gunk in the eye and they’ve actually shown that vision has been improved in several of the patients so far.
Okay, so some of the things that are in development are a cell therapy for Parkinson’s disease. Parkinson’s disease is caused by the death of a particular type of neuron called a dopamine neuron, which is in this tiny little part of the brain called the substantia nigra, it’s about the size of a walnut. By the time a person has Parkinson’s disease, they have symptoms, at least half of those cells are already dead. So in this particular case there’s no strategy that would allow you to have a normal life just by rescuing the cells you have left. So our strategy is to generate dopamine neurons that can be used to transplant back into the patients with Parkinson’s disease. There’s a long history here, which I don’t have time to tell you about but there’s a reasonable chance that this will work because there’s been a long history of using fetal cells and then using other cell types as transplants for Parkinson’s disease. So we’ve selected eight patients, we’ve made induced pluripotent stem cells from them, we intend to transplant, to make those into dopamine neurons, transplant them back to their brains and they should not be rejected because they’re exactly the same, they came from the individuals.
Another technology that we’re developing is a treatment for multiple sclerosis. Multiple sclerosis is caused by an immune attack on the glial cells that wrap the neurons. So they screw up the messaging from the spinal cord to the muscles. It’s quite a very serious disease but people generally don’t die of it. Our pre-clinical research is based on something and the result I’m just about to show you and that was that we discovered that when we put human neural precursors, that’s really, really young neurons that haven’t decided exactly what they want to be yet, derived from embryonic stem cells or from induced pluripotent stem cells into the spinal cords of paralyzed mice. The mice got up and walked. So what our goal is is to identify what it is about those cells that allows them to work so well. Okay, so on the left you’ll see what the animals look like after they’ve been induced to have multiple sclerosis. They have to be fed by hand, they can’t move their hind limbs. And this is the result on this side, still looks a little jerky but that’s the film. So you can see the little clips on the back, that’s where we did the surgery and even after just three weeks after the transplant the mice are starting to look a lot better. And then if you look six months after the transplant the controls sometimes get a little bit better or the other one there is getting no better whatsoever and then after they get the transplant the mice look almost normal. There’s a little bit of paralysis in their tails but otherwise they’re perfectly fine. So this was a discovery that led us to launch an entirely new program to try to find out what these cells did, how did they work because we hadn’t a clue. So right now we’re becoming protein biochemists so that we can identify what proteins were made by those cells that led to this long-term recovery.
Okay, so to summarize the things that we know are that hundreds of unregulated stem cell clinics are experimenting on humans for profit. There are at least two, there are two different kinds of stem cells. There are the adult stem cells that can’t cure anything and there are pluripotent stem cells that can give rise to everything in the body. Carefully designed stem cell therapies are now in clinical trials or in pre-clinical development. It seems like we’ve been waiting a long time but the dam has burst and now these things are moving into the clinic. And many of these diseases have planned clinical trials using these cells. Some of the things that we don’t know is when these therapies will be available. They’re being tested by the FDA, that may take years, I hope it doesn’t, but eventually the process will get quicker. We don’t know whether all these therapies are going to be successful. There are different issues for different diseases. And then finally, we don’t know where the funding is going to come from because there’s too much uncertainty for either pharma or biotech to invest. And we’ve come to rely on philanthropy because we are deep in the valley of death right now. We cannot transition to the clinic without more funding. And this is one of the funding organizations that we founded with the help of the Parkinson’s Association of San Diego and it involved the eight patients that I told you about, they are helping us fundraise, their families are helping us fundraise and so far we’ve raised about $1.5, $1.6 million dollars just from 900 people in Southern California.
Okay, so I want thank you for listening to this and I also want to thank my lab. The images down on the bottom are all images that were taken by people in that picture and we have one of our campaigns right now is to do huge blow ups of some of these pictures and provide them to our donors as gifts and thank yous. Thank you.


Jeanne F. Loring

Professor and Director, Center for Regenerative Medicine, Dept. of Chemical Physiology, The Scripps Research Institute

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