Ott Lab, Massachusetts General Hospital

Gallery: Rat limb grown from cells in the lab, and primate limbs are next Gallery Gallery: Rat limb grown from cells in the lab, and primate limbs are next + 1



A semi-functional rat forelimb has been grown in the lab -- and primate limbs are next.


A team of regenerative medicine scientists and surgeons at Massachusetts General Hospital (MGH) used a decellularisation approach -- already commonly used for growing tiny artificial organs -- for the pioneering research.

Experiments growing kidneys, livers and lungs have already been successful, resulting in a 0.5mm x 4mm "liver" to a working kidney that successfully filtered blood and urine when transplanted to a rat. As with the latest rat limb study, all of these experiments have a longterm goal of developing a superior alternative to transplants, which have a high chance of being rejected and require recipients to take immunosuppressants for the rest of their life. An organ or limb grown from your own cells, would not pose such problems.

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Dr Harald Ott, who headed up the 2013 kidney-rat experiment, is also behind the current rat limb success. He helped grow the rat forearm using techniques he honed back in 2008. These involve stripping an organ of all its cells using a detergent, but leaving the membrane scaffold intact so progenitor cells can be transplanted onto it and encouraged to grow.

While prior organ experiments would naturally require the use of progenitor cells useful in kidneys or livers, the latest rat study focussed on the cells that would be needed to rebuild a limb from scratch, particularly muscle and vascular progenitor cells. "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," said Ott in a statement. In the case of the rat forearm, the matrix (or scaffold) was made by stripping the cells from the limb of a deceased rat. It took a week for the cells to fully disintegrate and be shed, leaving behind the collagen structures Ott listed -- tendons, blood vessels and alike. During this period, the muscular and vascular progenitor cells were being grown as a culture. When the limb was ready and prepped, the endothelial cells were injected into the blood vessels and muscle cells were injected into the main body of the scaffold.

The prepped limb, filled with newly grown cells, was then popped in a bioreactor where it received nutrients, oxygen and electrical stimulation.


Two weeks later, and the world's first regrown rat forearm had been created -- up to a point, biologically speaking. When the new muscles were stimulated with electricity they would contract at the strength equivalent to about 80 percent of a newborn's, with joints flexing away and paws clenching. Blood also filled the new vascular system and circulated when the limb was attached to healthy rats (the rats were unconscious for this procedure). Skin grafts were also used to complete the limb.

Before moving onto baboon limbs (Ott and co have already decellularised one to prove they can, and introduced human cells to its empty blood vessels) nerves present the greatest challenge. The whole point of the work being done at MGH is to craft a genuine replacement for the prosthetics being used by humans today. As the team points out in a paper published in Biomaterials: "An autologous, bio-artificial graft based on native extracellular matrix and patient derived cells could be produced on demand and would not require immunosuppression after transplantation." Without nerves in place to alert a transplant recipient to pain, any replacement limb would be severely lacking. "In clinical limb transplantation, nerves do grow back into the graft, enabling both motion and sensation, and we have learned that this process is largely guided by the nerve matrix within the graft," commented Ott. "We hope in future work to show that the same will apply to bioartificial grafts. 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."

Blood vessels will also prove a challenge -- the short lifespan of most organs grown in the lab to date is largely due to the matter not getting the oxygen and nutrients it needs and would ordinarily get from a flourishing network of vessels.

While baboons will be up next, Ott told the New Scientist anything would do, from legs and arms to "other extremities".