Tuesday, July 29, 2008

Stem cell scientist predicts health revolution


Stem cell czar: UM researcher leads alternative effort

ftasker@MiamiHerald.com

Dr. Joshua Hare believes medicine is close to a goal long thought to be impossible: healing the human heart.

The way to get there? Stem cells.

''These could be as big as antibiotics were in the last century,'' says Hare, the researcher heading up the University of Miami's new Stem Cell Institute. ``Stem cells have the potential to have that kind of impact. Diseases like heart attacks, strokes, kidney failure, liver failure -- we will be able to transition them into things you live with.''

Hare spends his days peering through powerful microscopes, recruiting scientists from top universities and attending to patients betting on improving their conditions through his clinical trials.

Stem cells, only one-thousandth the size of a grain of sand, are the master cells of the body -- the source from which all other cells are created.

The most basic are embryonic stem cells, which are ''totipotent,'' meaning they can divide into any other type of cell -- heart tissue, brain tissue, kidney tissue -- all 220 cells that exist in the human body. They're controversial because when they are harvested, the embryo is destroyed, ending potential life.

But coming into view are new kinds of stem cells -- immature adult stem cells that can be extracted from bone marrow, from organs such as the heart or kidney or even from the skin. These can be taken without destroying embryos.

While researchers until recently believed adult stem cells were limited because they could develop only into cells similar to them -- bone marrow cells only into blood cells, for example -- evidence is growing that they, too, may become the tissue for hearts, brains, kidneys and other organs.

Here are the three sources of adult stem cells and their varying potentials:

Bone marrow stem cells: These are considered ''multipotent.'' Most researchers believe they can become heart tissue. Some feel they also can change themselves into kidney, brain or other organ cells -- although perhaps not all organs.

Organ stem cells: These cells are taken from tissue in hearts, kidneys and other organs. Some researchers believe they are also ''multipotent,'' meaning that a heart stem cell can turn into a brain or kidney or other cell, although not all 220 of the body's cells.

Skin cells: Stem cells taken from the skin, with genetic modification, may also be ''totipotent'' -- just as able as embryonic stem cells to turn into all 220 types of cells in the human body, new research indicates.


Dr. Hare expounds on these developments:

Q. You've said that the basic idea behind your stem cell work is that a healthy human body is creating stem cells all the time to keep its organs healthy, and you're trying to tap into this ability to expand its powers?

A: That's the theory. It does sound fantastic. Actually, it happens in the body all the time, in tiny amounts. In our blood, to survive, we have red blood cells that carry oxygen, white cells that regulate the immune system and platelets, which are tiny cells that seal off cuts. They come from stem cells in the bone marrow. [The marrow is the source for all red blood cells, platelets and some white blood cells.]

The cells circulate in the blood all the time. Unless there's a signal that says, 'Come here and do this,' they will just keep circulating. If you get a cut, the cells will be recruited to that area to do what they do.

Q:Could such cells heal a heart attack all by themselves?

A: Experts believe the ability of the body to heal itself without help is limited. The system can slowly replace missing cells here and there, over a lifetime. But it's not designed to repair a massive injury like a heart attack. That's where we as doctors can intervene.

Q: In fact, you are intervening. You've led two studies at Johns Hopkins University and University of Miami in which you have harvested immature, or ''mesenchymal'' adult stem cells from the bone marrow, multiplied them many times in the lab, then injected them into the damaged heart. Is the idea that the bone marrow stem cells become heart cells?

A: This is where the biology gets somewhat murky. We don't understand all the elements. We do have evidence that the cells differentiate [develop] into healthy heart tissue.

Q:And this could be true with a damaged liver, kidney or brain?

A: In theory.

Q: And, while so far you've had to inject the bone marrow stem cells directly into the heart duringsurgery, you now have FDA approval for using a catheter to inject the stem cells via the groin?

A: That's right.

Q:You've said other kinds of adult stem cells are at work too?

Hare: Many cells are involved in the body's attempts to heal itself. Some are from blood cells from bone marrow. But also, within the organs themselves, there are resident precursor cells that are stem cells. They're sitting there like front-line soldiers in an injury. We think those cells form collections that talk to each other and can go out and do healing. So we are engaging in a new study that will look at cardiac stem cells.

We can take pieces [of heart tissue] during surgery, multiply the stem cells in the lab and have a large amount we can give back to the patient.

Q: Could an organ stem cell from, say, heart tissue, become a stem cell in the brain or kidney?

A: It's possible, but not certain. We're interested in studying how many degrees of freedom these cells have.

Q: And now researchers are getting stem cells even from the skin?

A: We're starting to look at that. We know that stem cells in the skin replenish every 120 days. Researchers a year ago took regular stem cells from the skin and genetically reprogrammed them by introducing four genes. They were able to turn them into stem cells with a nearly unlimited capacity.

Q:If this works, won't it do away with the need for embryonic stem cells?

A: There are lots of problems with it. It's a genetic modification. Whenever you do that, it introduces a whole new area of concern. Recent reports say animals treated with these cells have a very high risk of cancer.

Q: If embryonic stem cells do turn out to be best, will it be because they are the best at differentiating -- that is, turning into other kinds of cells?

A: Exactly right. That's the theoretical reason they should be best, and there are stats that back that up. An embryonic stem cell is at a state that it can make a whole organism. You can make a whole mouse out of an embryonic stem cell. There are 220 cells in the human body, and embryonic stem cells can make each and every one of them.

The issue I've always worried about is do you want to make every cell in the body. That could increase the risk of cancer. What I like about our approach is that it is targeted. We're trying to heal the heart.

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