Scientists are now paving the way for limb regeneration and bioengineered transplants as a Massachusetts General Hospital research team has succeeded in growing a rat limb in the laboratory.
Published in the scientific journal Biomaterials, the team’s work details how it was possible to grow a limb from scratch, in vitro.
Losing a limb is particularly difficult for any individual. More than 1.5 million Americans area already going through the struggle and although prosthetic limbs are an option, they rarely come without discomfort. Granted, their function and appearance has improved greatly. Robotic limbs are now being tested in clinical trials but despite the ever-growing sophistication, there are many other limitations.
That’s why scientists have pursued human limb transplant, particularly when using the patient’s biologic material could one day become reality.
The team of Mass Gen Hospital managed to prove this concept. They grew the limb of a rat, including all of its muscular tissue and vascular structures (functioning veins and arteries). Dr. Harald Ott, the leading author of the paper, described the difficulties making (or one day growing) a functional replacement:
“Limbs contain muscles, bone, cartilage, blood vessels, tendons, ligaments and nerves — each of which has to be rebuilt and requires a specific supporting structure called the matrix.”
Bio Engineered Limbs -The Future of Regenerative Medicine
Other types of transplants have been attempted, for instance hand transplants from donors. But as with any type of transplant, there are many hoops to jump through and the lifelong immuno-suppressive therapy that patients have to adhere to is also a downside.
What the research team at the MGH’s Department of Surgery and Regenerative Medicine Center discovered was that a matrix was sustainable long enough to ensure that the normal tissues belonging to a limb could form and be cultured. They also showed that it is possible to repopulate both the muscles and the vascular structures of such a lab-grown limb.
When a patient’s own cells are used to regenerate a limb (rather than rely on donor material) the risk of rejection as well as the lifelong need for immuno-suppressive medication is eliminated. Scientists had already managed to grow muscle tissue and veins in a lab by using the patient’s own cells or stem cells.
Remarkably, though, it’s the first time that entire limbs were successfully grown. The team intended to strip down the donor organ so as to obtain the matrix that Dr. Ott had mentioned. Once all cells had been removed, scientists used the neutral matrix as support for the later development of the limb.
This matrix serves as a structure where specialized cells can be embedded. And each such matrix may be populated with the patient’s own cells.
Other teams of researchers used the same concept to grow kidneys, lungs, livers or hearts (in animal models). But growing a complete appendage, a limb, is the most complex achievement yet.
Researchers Create Lab-Grown Extremities
The team used deceased rats, whose limbs were stripped down to the matrix Dr. Ott was referring to. By only preserving the nerve matrix and vasculature, scientists were then able to provide the necessary structures to support the tissues required by the limb.
Basically, researchers injected vascular cells into the limb’s main artery. Other progenitor cells were injected in specific places along the matrix, corresponding to the positions of different muscles. For five days, the limb received electric stimulation aimed to encourage muscle development.
A progenitor cell represents a mid-point state between fully differentiated cells and stem cells. They are capable of forming one or more different types of cells. This soon-to-be lab-grown limb was then placed in a bioreactor filled with a nutrient solution.
In a couple of weeks, the team of researchers had obtained a limb that, when electrically stimulated, was capable of contracting with 80% of the strength that a normal newborn rat’s limb would be capable of.
But the team didn’t stop there. Soon after, they attempted to transplant the bioengineered limbs. The lab-grown limbs were transplanted into recipient laboratory rats and soon after the procedure, blood was circulating through the limb. Additionally, electrical stimulation of the graft produced appropriate responses in the limb’s joints.
Such biotechnology could have endless possibilities. For one, patients would no longer be incapable of gauging pressure or heat if such a limb were transplanted instead of a robotic one.
Further Research Possibilities
And though clinical trials still have a long way to go, this discovery heralds a completely new horizon for amputees. Because in such situations, nerves would grow back into the graft, patients would be capable of not only motion but also sensation. Dr. Ott explains that the process is supported by the graft’s nerve matrix.
The team now hopes to repeat its results with human cells and successfully replicate other tissues such as cartilage, bone and connective tissue. Initial attempts at decellularizing baboon forearms were successful, so it seems that the researchers are on the right track.
Image Source: CNET
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