In Massachusetts Lab, Scientists Grow An Artificial Rat Limb
A team of scientists at Massachusetts General Hospital in Boston made news earlier this month when they published research in the journal Biomaterials describing how they'd created the world's first bioartificial limb in the laboratory.
Or, in other words: scientists have now grown the entire forelimb of a rat in a lab.
Dr. Harold Ott, head of the Ott Laboratory for Organ Engineering and Regeneration, and his team were able to "engineer rat forelimbs with functioning vascular and muscle tissue," according to the hospital.
The scientists used a process called decellularization. They removed the living tissue from an existing rat limb, leaving just a "framework" — made of things like proteins — behind. Then they re-populated that "scaffolding" with new, living cells.
This may be an important first step leading to the eventual creation of functional, bioartificial limbs that could be used in transplants. That could be a step up from existing prosthetic devices.
"The loss of an extremity is a disastrous injury with tremendous impact on a patient's life," Ott and his colleagues wrote in Biomaterials. "Current mechanical prostheses are technically highly sophisticated, but only partially replace physiologic function and aesthetic appearance."
And while the decellularization process isn't new, growing a limb is.
"[Ott's] team and others at MGH and elsewhere have used this decellularization technique to regenerate kidneys, livers, hearts and lungs from animal models, but this is the first reported use to engineer the more complex tissues of a bioartificial limb," the hospital said in a press release.
Ott tells NPR's Arun Rath that his team's work "finally proved that we can regenerate functional muscle." (They know because they ran an electrical current through the muscle tissue — and the little rat limb began to twitch).
They've since applied the first part of this technology — stripping cells from the framework — to the arms of primates, showing the process might work on the human scale.
Interview Highlights
On what they accomplished
I think this is a very exciting time right now because basically what we can do is we can push cells to become heart cells or muscle cells, but we're not quite there yet to then guide them to grow into a full-blown heart, lung, kidney or in our case, a forearm. It's just highly complex and it's hard to do in a dish.
In our study, we basically provide a shortcut through that process by providing a blueprint for these cells. ... We isolate this scaffolding and then ... after moving all dead cells out, we repopulate this framework with new, living cells, and thereby turn little muscle cells into functional muscle in the context of a composite tissue. ...
The forelimb itself was not moving in the study yet. We got to the point where we were able to explant muscles — so, take muscles from this forelimb — and those were moving again. So those little muscles were not strong enough yet to move the entire arm, but they were strong enough to move on their own and to have measurable contractile force.
On how it felt to succeed in the experiment
It was certainly exciting when we saw these myofibers contract for the first time. ... Bernhard Jank has been the postdoctoral fellow who has been working on this project for four years, and I can't tell you how excited he was — because it finally proved that we can regenerate functional muscle on this matrix. So that the fact that we saw these little muscle fibers contract in a dish really showed us that this is a platform that eventually has the potential to regenerate functional composite tissue for patients.
On how these technology can be used next
The next steps are to scale the process of scaffold generation to human tissue. ... This technology can be applied to at least generate the framework of a human-scale scaffold or human-scale graft. The next step will be now to apply the cellular part ... to human- or patient-derived cells and to answer quite a bit more questions.
As you can imagine, this scaffold not only has to be alive — but eventually, we hope that it will connect back to the patients through recipients' nerve system[s] in order to become fully functional.
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Transcript
ARUN RATH, HOST:
We're now a step closer to being able to grow replacement parts for our own bodies. In their lab at the Massachusetts General Hospital, Dr. Harold Ott and his team have grown the entire forelimb of a rat.
HAROLD OTT: I think this is a very exciting right now, because basically what we can do is we can push cells to become hard cells or muscle cells. But we're not quite there yet to then guide them to grow into a full-blown heart or lung. It's just highly complex. And it's hard to do in a dish.
RATH: The scientists use a process called decellularization. They remove the existing living tissue from an existing rat arm and repopulate the scaffolding left behind with new, living cells. And the arm they've created looks disturbingly real. You can check out the photos on our website - flesh, muscles, everything. That's not all. They ran an electrical current through the muscles tissue and the little arm began to twitch.
OTT: Those muscles - those little muscles were not strong enough yet to move the entire arm. But they were strong enough to move on their own and to have measurable contractile force.
(SOUNDBITE OF FILM, "FRANKENSTEIN")
COLIN CLIVE: (As Henry Frankenstein) It's alive. It's alive. It's alive.
RATH: OK, so Dr. Ott didn't quite flip out in Dr. Frankenstein fashion, but he is very excited about his creation.
OTT: Because it finally proved that we can regenerate functional muscle on this matrix. It sort of really showed us that this is a platform that eventually has the potential to regenerate functional composite tissue for patients.
RATH: Now that they've created the arm, Dr. Ott says it's time to work on making the limb re-attachable and fully functional.
OTT: The next step will be now to apply the cellular part to the cell technology of this paper to human or patient-derived cells and to answer quite a bit more questions. As you can imagine, this scaffold not only has to be alive, but eventually, we hope that it will connect back to the patients through recipients' nerve system in order to become fully functional.
RATH: They've since applied this technology to arms of primates in hopes of building a framework on the human scale. Transcript provided by NPR, Copyright NPR.
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