Stem Cell Research in Multiple Sclerosis

In this video, Mark S. Freedman, MSc, MD, CSPQ, FANA, FAAN, FRCPC, Senior Scientist, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada, recaps his Neurology Week presentations, which discussed stem cell research for the treatment of multiple sclerosis (MS). 

Read the Transcript:

Dr Freedman:  Hello, everyone. I am Mark Freedman. I'm a professor of neurology at the University of Ottawa and a senior scientist at the Ottawa Hospital Research Institute in Ottawa, Ontario, Canada.

I'm recapping for you a couple of topics that I will be discussing during Neurology Week, with a focus on stem cells and their use, in particular in multiple sclerosis.

I will be doing a general lecture on stem cells to know what they are, where they come from, how they're derived, what the problems are in using them, and home in a little bit more on the use of blood-derived stem cells or hematopoietic stem cells.

It's an important topic because everyone thinks the stem cells are the cure-all for everything, and indeed they have an incredible potential. Since we discovered everyone has them, they can actually be found in many different organ systems.

In particular, they have the propensity to become anything that the body desires it to be since they are primordial. They're the first cell that probably derives from a fertilized embryo.

We know that the embryos at a certain stage are just a big mass of cells that don't look like anything. Nature has its own magic in directing certain cells along the pathway to become a brain cell, a heart cell, a lung cell or whatever.

That magic has yet to be uncovered, but there are ways in which we can manipulate the cells outside the body and actually direct them along certain differentiation pathways, mimicking perhaps the way the nature does it.

The idea that you can take a cell from, of course, a basic embryo and then grow heart cells or pancreas cells or brain cells, and then perhaps use them to replace damaged tissue is what we're hoping the world will derive from all this. The reality is that hasn't happened and there are lots of reasons for it.

Embryonic cells and their use is very controversial. Certain countries won't allow it. It's against religion or ethics, and so they've come to a pretty well standstill in the use of embryonic stem cells.

The other important aspect is that embryonic stem cells are not a match the host. A lot of mothers who think that they can save their embryonic cells from their fetus or cells from their placenta and use them for themselves, they don't recognize the fact that the genetics are different.

They share only a quarter of the chromosome, so they actually could completely reject the cells. The host would have to then be immunosuppressed.

The whole idea would be to match completely the cell that you're driving to the genetic makeup of the host, and there's no rejection. Still, it comes back to regrow the cells outside the body, and we put them back in. Who's to say that they're going to do what we hope they are going to do?

They don't just naturally get in place and become the cell that you're hoping they're going to do because that damaged tissue grew with it, with the being and learned to do what it was supposed to do.

We've learned that the hard way that we put the brain tissue into the brain, it just sits there. It doesn't really become what you're hoping it to do, and sometimes it just grows with no real boundaries, and that forms small tumors that we call teratomas.

Getting the cells outside of the body, differentiating them is not magic anymore. We can do this quite readily, but getting them into the body and getting them to do what we want them to do, either to replace damaged tissue in the case of, say, insulin-secreting cells for the pancreas we put them in there.

Then they're going to behave just like the body's own insulin, making cells and diabetics will be cured tomorrow. That hasn't happened. We're now recognizing there're some severe limitations in the use of the stem cells.

There's one particular group of cells called induced pluripotent stem cells, which you can take a cell from any part of the body, even your cheek cell, and using certain factors…these factors can actually transform the cell back to being a primordial stem cell, and then we can redirect it along the differentiation pathways.

The problem is one of those factors is an oncogene, which causes or can cause cancer. That is not something that we can do readily, although the scientists have been using this for a while to grow cells from the same animal, put them back in, and do experiments. That is also helping some human research.

If you can imagine a patient with MS, we're trying to grow brain cells interact them say with their immune cells. We can grow their cells and do these immune interactions in the same genetic compatibility frame, but we can't, at this point, put them back into people because of the transformation factors that we're using.

It boils down to then what kind of stem cells can we use? The hematopoietic stem cells, in fact, were the first ones ever discovered. They're the ones that are readily used and can be readily used for treatments.

That forms two types of treatments that we've been able to do more successfully in the patients who have very aggressive and active disease. We've been able to completely eliminate their diseased immune system, the one that's causing all the problems, and regrow them from their own stem cells into being a fully competent hematopoietic system with all the red cells and white cells that normally make up the hematopoietic blood system as well as the immune system.

The interesting thing is, of course, when that regrows, patients no longer have active disease. It shuts it down, and many patients have actually shown some significant recoveries. They never have to go on to disease-modifying therapies after that, so a pretty incredible therapy.

The other, which is still very much in its early development and still very much a research topic, is the use of the mesenchymal stem cells. You get these from the same place. You can get it from a bone marrow aspirate. You can get them for fat tissue. In fact, you can get mesenchymal stem cells from many sources.

We have the ability to grow these outside the body and in a very purified form, we can redeliver them. There's different ways of doing that. Most of those people just redeliver them using intravenous injections.

They have the ability to home to areas of damage. Through many different properties, they can encourage repair or protection of that organ if it turns out to be something that's actively being damaged.

This is really where it's being focused upon. They do have the potential for coming, a primordial cell and differentiating into what you want, but it's not likely that that occurs in nature and can't be exploited for the purposes of treatments. Those are mesenchymal stem cell transplantation trials.

We've just completed a major one and a multicenter study, which is showing that they're safe to be able to give them intravenously. Some groups have actually injected them directly into the spinal fluid. A little more complicated because if you have to do repeated lumbar punctures, it's not necessarily the greatest thing for patients.

There is the potential for the intravenous therapy to move forward. Those are the two main ways in which stem cells are being used today.

We're hoping some of the other types of research will generate cells that will help us in the future. The big caution here is that there are a lot of groups in the world who are preying upon our patients and claiming that they're able to derive these cells and that they're going to cure their disease. They're in it for the money.

They're in it to make a lot of money, and desperate people will do desperate things. They have not proven that they can do anything other than the fact that they can pull some cells out of your body, maybe purify them in the morning and give them to you in the afternoon.

In order to generate enough mesenchymal stem cells, you need good two to three weeks in a proper cell facility. This is a very expensive venture, not something that these fly-by-night centers want to get involved with their use.

That's the word of caution, but the positives have come out of the bone marrow transplant studies now doing worldwide. All nations that are capable of doing it or offering it as a treatment option. For aggressive patients, the mesenchymal stem cell transplantation, still very much in its early research phase, but we're hopeful.