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The Power of the Stem Cell
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By Erica Heilman

The volatile debate about human embryonic stem cell research continues to rage. But in order to fully understand the ethical and political implications surrounding this research, it is important to first understand the science. What makes stem cells so special? And how do these elusive cells stand to revolutionize the practice of medicine?

Below, hematologist Dr. Robert Marcus, of Addenbrooke's Hospital in Cambridge, UK, introduces us to the power and potential of the human stem cell.

First, what are stem cells, and where are they found?
DR. ROBERT MARCUS: Stem cells are the basic seed cells of the body. In the same way that seeds turn into flowers, stem cells turn into the mature cells that perform the functions of all the organs and tissues in the body. These cells in adult life are found mainly in the bone marrow.

What is so exciting about these stem cells that live in the bone marrow?
They are pluripotent, which means that they can become something else. When these stem cells are added to certain growth factors and chemicals, they might be able to turn into brain cells or heart cells, to replace those that are damaged. We are already seeing this in animal studies. If we can take cells from the bone marrow and restore their pluripotential qualities, in other words, turn them into muscle, or brain, or heart, or gut cells, then we can repair defective organs with those stem cells. That's why they are potentially so important.

What kinds of diseases could be treated with this type of cell therapy?
The main interest right now is in brain disease and spinal cord disease. If the spinal cord is cut, patients become paraplegic. They're unable to walk. And at the moment, there are no methods to make these nerve cells regrow to restore power to the legs or arms of patients who are paralyzed. Once you've become paraplegic from spinal injury, as with Christopher Reeves, there is no possibility of the cells spontaneously growing back.

If we could turn bone marrow cells into nerve stem cells, then we might be able to restore the population of nerve cells, heal the spinal cord, and reverse paralysis. The same goes for brain tissue. Using stem cell therapy, we might be able to replace degenerated or damaged brain tissue in diseases like Parkinson's and Alzheimer's.

Have we seen any success yet?
Not at the human level, but certainly in animal models. There is the potential to improve heart muscle cells and brain cells in mice -- by injecting stem cells derived from the bone marrow. And that's a very exciting prospect.

Let's take Christopher Reeves as an example. Could you describe how stem cell therapy might work with spinal cord injury patients?
You would take stem cells from the bone marrow or blood of the patient, and incubate those purified stem cells with nerve growth factors in an attempt to get those stem cells to turn into nerve cells and tissue. The idea would be to implant those cells into the area of defect in the spinal cord, and hope they would grow.

Why couldn't you find nerve stem cells to re-populate the nerve cells? Why must the stem cells be harvested from the bone marrow?
Because in each organ, the cells have differentiated, or grown up to become mature cells that carry on the functions of that organ. They can't turn back, and they can't actually renew themselves. There are no stem cells in the brain, for example, or in the heart.

It's only in the human fetus that cells retain true totipotentiality, in other words, we know that they can turn into any kind of cell in the body.

What is the difference between adult stem cells and embryonic stem cells?
Stem cells derived from early embryos are "totipotent," which means that they can become any cell type in the body. After all, people start out as a single fertilized egg. That single cell begins a process of cell division that results in all the different cells of the body.

As the embryo grows into a fetus and then a baby, the potentiality, or the flexibility of those stem cells, diminishes. We're not certain yet whether adult stem cells, or cord blood cells, which are also rich in stem cells, will be flexible enough to repair brain cells, for example, or heart muscle cells. That's why there is major interest in embryonic stem cells.

In your opinion, do embryonic stem cells play a central role in the development of new cell therapies?
I think it's quite possible. In the UK there have been two centers designated for embryonic stem cell banks, suggesting that we are beginning to recognize their potential. Now we don't know of course whether they will fulfill that potential, but I think that those stem cell banks will be very valuable indeed.

Do you think that stem cell therapy is going to become viable in the near future?
Stem cell transplantation has already proven successful in leukemia, where we use it to restore blood production after high-dose chemotherapy. We have been doing this for twenty years.

And as we continue to get a clearer understanding of stem cell biology, we are beginning to see how stem cells derived from marrow cells or blood cells or embryonic cells might be used to repair damaged hearts or brains. I think that's potentially very exciting. When it will happen is not certain. I think it could be between five and ten years away. But I might be too pessimistic there.

Do you think that we should be cautious in our progress?
I do. I think that in terms of gene transfer, which is a process of inserting genetic material into the stem cells to try and treat genetic disease, we should be cautious. We should be cautious with hybridization experiments, and with cloning as well. Any time you transfer genes within the cloning process, or change the genetic material within a cell, there may be defects introduced into a natural organ or species development. I think I would be quite cautious there.

But in terms of differentiating embryonic stem cells and adult stem cells into different kinds of cells -- liver, heart, lung, brain -- I would be less cautious there. I think the potential for damage or danger is much more limited.

Dr Robert Marcus is Consultant Hematologist at Addenbrooke's Hospital, Cambridge, UK and Director of the East Anglia Bone Marrow Transplant Unit

Published on: 2002-03-20
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