IT MIGHT look like an amputated rat forelimb, but the photo above is of something much more exciting: the limb has been grown in the lab from living cells. It may go down in history as the first step to creating real, biologically functional limbs for amputees.

"We're focusing on the forearm and hand to use it as a model system and proof of principle," says Harald Ott of Massachusetts General Hospital in Boston, who grew the limb. "But the techniques would apply equally to legs, arms and other extremities."

"This is science fiction coming to life," says Daniel Weiss at the University of Vermont College of Medicine in Burlington, who works on lung regeneration. "It's a very exciting development, but the challenge will be to create a functioning limb."

A biolimb would get round many of these obstacles as it only contains cells from the recipient so would avoid the need for immunosuppression. It should also look and behave naturally.

"This is the first attempt to make a biolimb, and I'm not aware of any other technology able to generate a composite tissue of this complexity," says Ott.

The technique behind the rat forelimb – dubbed "decel/recel" – has previously been used to build heartsMovie Camera, lungs and kidneysMovie Camera in the lab. Simpler organs such as windpipes and voicebox tissue have been built and transplanted into people with varying levels of success, but not without controversy (see "Rocky road to replacement organs").

In the first, decel step – short for decellularisation – organs from dead donors are treated with detergents that strip off the soft tissue, leaving just the "scaffold" of the organ, built mainly from the inert protein collagen. This retains all the intricate architecture of the original organ. In the case of the rat forearm, this included the collagen structures that make up blood vessels, tendons, muscles and bones.

In the second recel step the flesh of the organ is recellularised by seeding the scaffold with the relevant cells from the recipient. The scaffold is then nourished in a bioreactor, enabling new tissue to grow and colonise the scaffold.

Because none of the donor's soft tissue remains, the new organ won't be recognised as foreign and rejected by the recipient's immune system.

A forearm is much more difficult to create in this way than a windpipe, say, as a number of different cell types need to be grown. Ott began by suspending the decellularised forelimb in a bioreactor, plumbing the collagen artery into an artificial circulatory system to provide nutrients, oxygen and electrical stimulation to the limb. He then injected human endothelial cells into the collagen structures of blood vessels to recolonise the surfaces of blood vessels. This was important, he says, because it made the vessels more robust and prevented them from rupturing as fluids circulated.

Next, he injected a mixture of cells from mice that included myoblasts, the cells that grow into muscle, in the cavities of the scaffold normally occupied by muscle. In two to three weeks, the blood vessels and muscles had been rebuilt. Ott finished off the limb by coating the forelimbs with skin grafts (Biomaterials, doi.org/4w7).