In June,Harald Ott and his collegues of Massachusetts General Hospital researchers announced they’d built the first functioning lab-grown limb. The team amputated a dead rat’s forearm and chemically stripped away living cells, leaving behind what’s called the extracellular matrix, a kind of scaffolding for everything from blood vessels to nerve networks. The limb then spent two weeks growing muscular and vascular cells in a custom-built bioreactor. Electrical stimulation showed the resulting limb had a grip strength 80 percent that of a newborn rat’s. After being transplanted onto a living rat, the limb circulated blood through its new vessels.
Researchers from the Massachusetts General Hospital in the US have made a major breakthrough in the field of artificially grown body parts: the scientists have successfully grown a functioning rat limb using a technique that could eventually lead to fully natural replacements for human limbs.
Muscles and veins have previously been grown in laboratories, but up until now no one has repeated the trick with an entire limb because of the combination of different tissue types involved (muscles, bone, cartilage, tendons, blood vessels and so on). To solve the problem, scientists copied the technique already used for lab-grown organs.
The idea is simple.
- First, they take an arm from a dead rat and put it through a process of decellularization using detergents. This leaves behind a white scaffold. The scaffold is key because no artificial reconstructions come close to replicating the intricacies of a natural one.
- They seed the arm with human endothelial cells, which recolonize the surfaces of the blood vessels and make them more robust than rat endothelial cells would. Finally, scientists inject mice cells, such as myoblasts that grow into muscles. After two to three weeks, these cells use the scaffold to regrow the arm, on which rat skin is then grafted. Among the 100 rat forelimbs, he succeeded in recellularizing at least half.
- When Ott applies electrical pulses to activate the muscles, he is able to make the rat paw clench and unclench. He has also attached the biolimbs to anaesthetized rats, and saw that blood vessels functioned as he had hoped.
- Next, Ott has to show that the arms will develop a nervous system, which will allow the arm to be controlled by the recipient rat.
- This has been shown to work in hand transplants, but remains to be seen in biolimbs. Also, Ott needs to prove that, as the theory suggests, these limbs will indeed not be rejected by the rat without the use of drugs.
- If the above is successful, the next target would be a primate’s arm. Ott has already shown that they can be decellularized.
“We have shown that we can maintain the matrix of all of these tissues in their natural relationships to each other, that we can culture the entire construct over prolonged periods of time, and that we can repopulate the vascular system and musculature,” said Harald Ott MD, leader of the study.
“Additional next steps will be replicating our success in muscle regeneration with human cells and expanding that to other tissue types, such as bone, cartilage and connective tissue,” he added.
As you might expect, there’s still a lot of progress to be made before the same ideas can be transferred to growing a human limb, but the findings published in the journal Biomaterials are encouraging. For Ott and his team, the next goal is to repeat the procedure with a baboon before work begins on working out exactly how a lab-grown limb could be attached to a body with no adverse side effects.
There are all kinds of potential complications in trying to graft a living, functioning limb onto someone’s body – not least the reaction of the existing tissue – but as human hand transplants have proved, they’re not necessarily insurmountable. If scientists can make the process work then natural limb transplants would offer many advantages over the robotic prosthetics in use at the moment – the ability to feel heat and pressure, for example, plus a more natural learning process for the brain as it adjusts to the new appendage.
Source: New Scientist