Miracle Medicine: Doctors Help Vets Regrow Muscle

In classical mythology, Prometheus was chained to a rock, where a vulture pecked out his liver every day. It would have been nothing short of a catastrophe, but, this being mythology, the organ grew back every night. In fact, liver tissue actually will regenerate, if less than half the organ is removed. (That's why transplants are possible from living donors.) (Article continued below...)

Now science wants to do for other parts of your tired, aching body what mythology did for Prometheus (minus the vulture). Need a new knee, bladder or esophagus? Why not grow one? "We all did it once, in the womb," says Alan Russell, director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh.

Leading the charge are doctors like Stephen Badylak, director of the Center for Pre-Clinical Tissue Engineering at the McGowan Institute. Already his research techniques have been applied to more than 1.5 million patients needing new tissue to repair the rotator cuff or lower urinary tract. Now he's working with the Armed Forces Institute of Regenerative Medicine (AFIRM) on a program to regrow fingers and limbs lost in battle. He spoke with NEWSWEEK's Anne Underwood. Excerpts:

NEWSWEEK: Your work sounds like science fiction.
Stephen Badylak: Starfish, salamanders and newts can regrow a lost limb. Human fetuses can also regenerate many structures during the early stages of fetal development. But that ability diminishes or disappears by the time we're born. The question is why, because the information is still there in our DNA. We want to resurrect fetal wound healing.

Tell me about your work with AFIRM.
Because of innovative explosive devices, soldiers are returning from Iraq and Afghanistan with lost fingers, lost hands, lost limbs. The only treatment options now involve prosthetic devices. For a 20-year-old, the rest of life is impacted in a negative way. The Defense Department is approaching this in a Manhattan Project mode. It's put $100 million on the table to address these horrific problems from a regenerative-medicine standpoint.

Will you really be able to regrow fingers and limbs?
In the foreseeable future, I doubt it. Fingers and limbs are very complex. They include nerves, bone, skin, muscle and blood vessels. They're also large. Limb formation in a fetus is on a scale of a few millimeters. In a human, you're talking 20 pounds of flesh and bones.

But you've been able to regrow large portions of muscle.
A soldier in Texas had been injured by an explosive device in Afghanistan and lost a large portion of muscle in the upper portion of his leg. This loss significantly compromised his strength and range of motion and his ability to engage in normal activities. We helped regenerate a portion of that muscle, which is amazing. That never happens spontaneously. Over the next year, we'll treat another eight to 10 soldiers.

How much of the muscle has grown back?
The results might be considered modest by some standards, but they're significantly better than anything tried before. He's had maybe a 12 percent increase in muscle mass, as measured by CT scan, and a 7 to 10 percent increase in strength over a two-month period. He wants a second procedure.

What made him a good candidate for this treatment?
The part of the muscle at the hip was intact, and the part at the knee was intact, so we were just replacing the section in between. Once you get the process started, the body takes over.

How do you initiate the process?
There are a number of approaches to regenerative medicine. But the one I've been working with involves harvesting the extracellular matrix (ECM) from a pig bladder or intestine and placing it at the wound site.

I doubt most people know what the extracellular matrix is.
If you take the bladder or small intestine and scrape away all the cells, what you're left with is structural tissue like collagen and functional molecules such as growth factors. There are literally hundreds of these proteins, all housed in the ECM. They instruct cells on how to behave—whether to multiply or migrate or differentiate into different types of cells. They tell cells at the site of a wound what to do. Equally important, they recruit cells to the wound site that wouldn't normally be there, such as stem cells. I wouldn't be smart enough to put them all together, but I can harvest what nature has done.

How does tissue from a pig's small intestine communicate to human muscle?
That's a great question. Certain things are so important to mammalian survival that they are conserved across species. The amino acid sequences are either identical or else so close to those in humans that they deliver the same message.

And because the ECM contains no cells, you can implant it in a person without causing an immune reaction?

Is that enough to stimulate growth?
Simply placing the ECM at the site might get cells interested. But if you don't recreate the micro-environment needed for tissue growth, it won't happen. That means you need the right pH, oxygen, moisture and nutrients. You also have to apply the correct mechanical forces. An Achilles tendon, for example, has to bear weight. Without those signals, it will turn into loose connective tissue.

I know you don't like to talk about this, but working with a powdered version of ECM, you helped three people regrow the tips of fingers that were accidentally severed.
The tips of fingers sometimes regrow anyway, especially in children, so we can't prove this was because of our work. You would need a clinical trial.

Obviously, you didn't start by regenerating large muscles. You began with smaller applications, such as rotator-cuff repair.
The rotator cuff is the tendon group around the shoulder that holds the arm in place and allows it to move in different directions. When it tears, there's nothing a traditional surgeon can use to repair it now. It's like trying to sew back wet Kleenex. But when we implant ECM, the body treats it as a scaffold on which it can build. The body's own cells invade. The scaffold is gone within 75 days, as the body replaces it with its own tissue. More than 1.5 million patients have been helped with our ECM product Restore—and those of two other companies. It's not true regeneration, because we're using a scaffold. But it might be just as effective.

Can you see this becoming standard practice one day?
There are lots of clever new approaches to regenerative medicine. We're learning which therapies work best for which applications. I believe we will get there.

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