What appears to be the world's first biolimb, a rat forelimb, has been grown in the lab of Harald Ott of Massachusetts General Hospital in Boston.
(Rat forearm is first biolimb)
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...
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.
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).
But would the limb's muscles work? To find out, the team used electrical pulses to activate the muscles and found that the rat's paw could clench and unclench. "It showed we could flex and extend the hand," says Ott.
The first time I ever read about the idea that it might be possible to regrow limbs was in science fiction writer Frank Herbert's 1972 uneven but highly readable novel The Godmakers, in which a badly injured agent is able to regrow what was lost:
Orne began to show small but steady signs of recovery... they placed him on an atlotl/gibiril regimen, forcing the energy transfer which allowed him to regrow his lost fingers and eye, restore his scalp line and erase the other internal-external damage.
(Read more about Frank Herbert's Atlotl/Gibiril Regimen)