Once you have the cells, you need to steer the way they grow and specialise. That means getting the right balance of temperature, pH, hormones, and more. It also means exposing growing tissues to the forces they would normally experience inside the body. Engineered arteries need to experience pulses of pressure that simulate the blood that normally pumps through them. Engineered muscle needs to be stretched. Engineered lungs need to feel a regular flow of air. “Every cell has the right genetic information to create the organ. You just need to put them in the right environment,” says Atala.
We can build you
The cells also need to grow along the right shapes, so getting the right scaffold is essential. For simple organs, like Beyene’s windpipe, it is possible to fabricate the whole scaffold from scratch. But solid organs have more complex shapes, so some teams start with existing organs, taken either from cadavers or from animals. They use detergents to strip away the cells, leaving behind a natural scaffold of connective tissues and blood vessels, which can then be seeded with a patient’s stem cells. It is the equivalent of stripping a building down to its frame and filling the walls back in. Scientists have made livers, lungs and even beating hearts in this way, and some have started to transplant their organs into animals.
Some researchers are excited by the potential organ-building capabilities of three-dimensional (3-D) printers. These devices are modified versions of everyday inkjet printers that squirt living cells rather than drops of ink. Layer by layer, they can make three-dimensional structures such as organs and, as of September last year, the blood vessels they contain. Atala is developing this technique – he wowed the audience at a TED conference last year by printing a kidney on stage (although not a functional one). He says, “For the level four organs, it’s just a matter of time,” says Atala. “We’re still a long way from full replacement, but I do believe that these technologies are achievable.”
Even after scientists successfully devise ways of growing organs, there are many logistical challenges to overcome before these isolated success stories can become everyday medical reality. “Can you manufacture them and grow them on large scales?” asks Robert Langer, a pioneer in the field. “Can you create them reproducibly? Can you preserve them [in the cold] so they have a reasonable shelf-life? There are a lot of very important engineering challenges to overcome.”
Doing so will take time, perhaps decades. Laura Niklason from Yale University first described how to engineer an artery in 1999, but these lab-grown vessels are only now ready for clinical trials in humans. If these simple tubes – just level two in Atala’s hierarchy – took a dozen years to advance, it is a fair bet that solid organs will take much longer.
But advance they will, driven in part by a substantial and growing medical need. “We’re doing a better job of keeping people alive longer, and the more you age, the more your organs tend to fail,” says Atala. “The number of patients on our transplant lists continues to increase, but the number of transplants performed remains flat. The need is only going to become more prominent as time goes on.”