Friday, December 16, 2011

Spare Parts for Humans: Tissue Engineers Aim for Lab-Grown Limbs, Lungs ?

Spare Parts for Humans: Tissue Engineers Aim for Lab-Grown Limbs, Lungs ?



JEFFREY BROWN: Next, research breakthroughs that seem almost like science fiction. It's all about growing human tissue and replacing or repairing muscles and, someday, even limbs.
NewsHour science correspondent Miles O'Brien has our story.
CPL. ISAIAS HERNANDEZ, U.S. Marine Corps: It looked like a chicken, like if you would take a bite out of it down to the bone.
MILES O'BRIEN: It happened in Iraq in 2004. He was badly injured in an artillery attack on his convoy.
CPL. ISAIAS HERNANDEZ: They patched it up because they said the other thank option would be amputation because they couldn't just leave my leg on with a hole in it.
DR. STEPHEN BADYLAK, McGowan Institute for Regenerative Medicine: You need people who think quantitatively and qualitatively working together on problems like this.
MILES O'BRIEN: What he did was reach out to this man. Dr. Steve Badylak is deputy director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, where they are in the vanguard of a fast-moving field called tissue engineering. The goal? Grow tissue or even whole organs to repair damaged or diseased human bodies.
Here, they are using pig bladders to help grow human muscle -- that's right, pig bladders. It turns out, they are a good source of a fundamental biological building block known as the extracellular matrix.
DR. STEPHEN BADYLAK: So, the matrix, the extracellular matrix -- we call it ECM -- is a sort of unique collection of structural and functional molecules that we then use as a therapeutic device to tell the body how to heal itself.
MILES O'BRIEN: ECM is like a magnet and a manual for the stem cells inside us. Scientists are not sure why, but the matrix lures those malleable cells and gives them the cues they need to, in this case, morph into muscle.
MILES O'BRIEN: The pillow.
DR. STEPHEN BADYLAK: We call this a powder pillow.
MILES O'BRIEN: The stem cells made their way to a pillow filled with powdered pig bladder matrix implanted in Corporal Hernandez's thigh in 2008. With the help of a lot of hard physical therapy from a very motivated Marine, they became muscle, a lot of muscle.
DR. STEPHEN BADYLAK: We never imagined we were going to get the robust response that we got. Now, he's replaced somewhere between 10 and 15 percent of his muscle mass at that site, but that muscle has gotten so strong that it's something like 50 percent of the strength of the quad.
MILES O'BRIEN: Badylak is starting a larger human trial.
So, using ECM, are you manufacturing body parts?
DR. STEPHEN BADYLAK: We're allowing the body to manufacture. We're setting the stage.
MILES O'BRIEN: Laura Niklason is doing just that in her lab at Yale University. So we can buy parts?
LAURA NIKLASON, Yale University: We have reached the point where we can buy parts. For simple tissues, we can buy parts.
MILES O'BRIEN: Niklason hopes the spare arteries and veins she has grown will be tested in human trials soon, but she is not stopping there. She and her team are growing living, breathing replacement rat lungs that are genetically tailored for a rejection-free transplant, because they are grown from the very cells of the recipient.
LAURA NIKLASON: Otherwise, you would be making a lung that would reject, just like the way lung transplants can reject now. So that's one of the major challenges with engineering a human lung, is we're going to have to learn enough and employ enough stem cell biology so that we can take stem cells from the patient and coax them to become all of the different cell types that we need to make a lung.
MILES O'BRIEN: The key to the coaxing process is our friend the extracellular matrix.
A matrix from a donor rat lung is bathed in cells that are genetically identical to the recipient. The cells marinate in an incubator called a bioreactor for seven days, creating a lung that is a perfect genetic match for the recipient.
If they're not breathing, they don't develop, essentially?
LAURA NIKLASON: Yeah.
MILES O'BRIEN: Unfortunately, the rat lungs she has grown and transplanted so far are short-lived. They fail within hours because of blood clots. Niklason isn't sure why. In fact, there is still a lot she is not sure of.
LAURA NIKLASON: That matrix has an enormous number of cues which we don't yet understand. But it directs the adhesion and the survival of cells within the lung. So, even though we deliver a mixture of cells into the lung, we find that they all go to their proper locations.
MILES O'BRIEN: It will be a long time before scientists will grow a breathing lung or a beating heart that could save a human life, but maybe not as long as you think.
DR. ANTHONY ATALA, Wake Forest Institute for Regenerative Medicine: When we started this, this was really still considered science fiction.
MILES O'BRIEN: Anthony Atala is director of the Wake Forest Institute for Regenerative Medicine. He's been at it for more than two decades. Now, he and his team are working on engineering more than 30 different tissues and organs, bladders and urethras, ears, skin, muscles, human liver tissue, and even a beating heart valve.
DR. ANTHONY ATALA: We know that, naturally, what a heart does is, it beats on its own. So, for us, the concept of recreating this in the laboratory is really nothing more than just recreating what nature already knows how to do.
MILES O'BRIEN: Atala makes it sound easy, but, of course, it is not. Humans do have the ability to regenerate. Our skin, for example, turns over every two weeks or so. But, over time, humans have also evolved to seal up disease and injuries with scars. It's good for keeping us alive after a trauma, but it prevents regeneration.
DR. DAVID GARDINER, University of California, Irvine: Just because we don't regenerate doesn't mean that we can't regenerate. It just means that we don't.
Now, what we have done here is change the information in the cells at the wound-site.
MILES O'BRIEN: Dr. David Gardiner of the University of California, Irvine, is trying to learn how to make humans better regenerators by studying nature's reigning regeneration champ: the salamander.
DR. DAVID GARDINER: When you cut off a salamander's arm, you can cut it off at any level. So, you can cut off fingers, you can cut off at the wrist or the arm or the elbow or the shoulder. And whatever you cut off, that's always what grows back. It doesn't grow back more and it doesn't grow back less.
MILES O'BRIEN: Gardiner wonders how a human who has lost a limb might be able to recover like a salamander.
DR. DAVID GARDINER: We do in fact have intrinsic regenerative abilities, just like the salamander does. It's just like two ends of the spectrum. We're not very good at regenerating complex organ structures like limbs or spinal cords and stuff like that.
MILES O'BRIEN: But there is some promising research on that front as well. Look at this before-and-after video. It's the same paralyzed rat. Its ability to walk greatly improved after cells like these were implanted near its spinal cord injury.
Aileen Anderson is an associate professor at the University of California, Irvine.
AILEEN ANDERSON, University of California, Irvine: What we know is that when we transplant these cells, we can restore the ability of animals with spinal cord injury to step. We can restore their ability to be coordinated.
MILES O'BRIEN: They are called neural stem cells, stem cells that are ideally suited to repair the central nervous system.
So, neural stem cells are more specialized?
AILEEN ANDERSON: Neural stem cells are more specialized. If you picture sort of a tree with embryonic stem cells at the trunk, and all the specialized cells that are relative to different organs like the brain or the spleen or your bone marrow, up in the branches, they become more and more specialized as you ascend.
MILES O'BRIEN: Anderson and her team are working toward clinical trials to inject neural stem cells into humans with spinal cord injuries.
Could these stem cells act like jumper cables? Maybe so.
AILEEN ANDERSON: Our hypothesis, our working plan here is that that restoration of circuitry is what's yielding the recovery of function.
MILES O'BRIEN: But you don't know for sure?
AILEEN ANDERSON: Nobody knows. How -- how many things do you know in science that you know for sure? We think we -- we think we know this because, if we transplant cells and let animals recover to a stable baseline, and then we selectively ablate the human cells that we transplanted, we lose the functional recovery.
MILES O'BRIEN: Francesco Clark is a big believer in the seemingly magical power of stem cells. In 2002, he dove into the shallow end of a pool.
FRANCESCO CLARK: And I was completely paralyzed in the blink of an eye.
MILES O'BRIEN: At first, he could not move a muscle or even breathe on his own. Over time, he has steadily improved, thanks to a tough regimen of physical therapy and, he says, three stem cell treatments he received in China and Germany. They are not yet approved in the U.S.
So, at this point, do you firmly believe there will be a cure for paralysis and that will derive out of stem cells treatments?
FRANCESCO CLARK: Absolutely. Yes, they're no doubt in my mind. I mean, I'm talking, I'm breathing, I'm moving my arms, I'm wiggling around, I'm getting stronger. It's just -- you want to say it's a matter of time, but it's not just time. There's a lot of effort that goes into it.
MILES O'BRIEN: So, how many years before we come back and see you walking around the house here?
FRANCESCO CLARK: I'm pushing for five years.
MILES O'BRIEN: For real?
FRANCESCO CLARK: Yeah.
MILES O'BRIEN: Like any Marine worth his salt, Isaias Hernandez is still pushing as well.
DR. STEPHEN BADYLAK: He's been such a warrior in more ways than one, that he deserves whatever we can give him. So, we're going to do one more surgery on Cpl. Hernandez. We're going to add more matrix and see if we can build more muscle for him and make him even better than he is today. So that's his future.
MILES O'BRIEN: How you feeling?
CPL. ISAIAS HERNANDEZ: Good.
MILES O'BRIEN: His goal for the future? A return to combat.
Why do you want to go back?
CPL. ISAIAS HERNANDEZ: Want to finish up at least a full tour -- if not, then just do everything to the best of my ability.
MILES O'BRIEN: We done yet?
CPL. ISAIAS HERNANDEZ: Depends on how long you want to ride for. Because these trails total, it's about 10 miles.
MILES O'BRIEN: How is the leg?
CPL. ISAIAS HERNANDEZ: Leg's good.
MILES O'BRIEN: Let's do it.
I am living, exhausted proof he already has plenty of ability, thanks in large part to an exploding field of science that may one day make us all live longer and stronger.


click for a brief video on tissues

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