Liver basting: After a scaffold is seeded with healthy liver cells, it is placed in an in vitro culture setup. The pink liquid circulating in the scaffold has the required nutrients to keep the cells alive. The scaffold has not yet been seeded with healthy cells.
The researchers also transplanted two-day-old reconstructed livers back into rats, connecting them to the animals’ vascular system. After eight hours, the livers continued to incorporate the animals’ blood flow and remained functional, something that had never before been done with such a complicated engineered organ. “It is very promising approach that will revolutionize the field of tissue engineering for livers,” Basak Uygun says. It’s a particularly challenging organ, because it requires constant and extensive blood circulation. “So if this could be done for livers, it’s major progress.”
“It’s very good work and it advances the field, showing more and more that these things can in fact be done and are possible,” says Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center, who has used both the ink-jet printing and decellularization approach. “Solid organs are incredibly complex, because they have a lot more cells per centimeter than any other tissue type. And how do you get blood supply to such a large volume of cells? Decellularized organs are a good strategy for preserving vascular tissue.”
There are, however, a few big obstacles remaining. The first problem is that the current method can’t quite repopulate the blood vessels densely enough to allow blood circulation for more than 24 hours. The exposed collagen of the scaffold causes the blood to coagulate and clot, which is why Uygun left the engineered livers transplanted for only eight hours.
The second obstacle will be finding a steady source for healthy human liver cells. In the nearer term, the researchers believe they can rely on cells from healthy donors. (Healthy livers can regenerate back to full size within just a few weeks.) But further down the line, stem-cell science may be advanced enough for people to donate their own cells, allowing scientists to differentiate them in the lab into liver cells that won’t induce an immune-system reaction and use those to seed a scaffold.
Korkut Uygun and his colleagues are already working on a solution to the blood-vessel problem, and believe they should have fully functional liver transplants in rats within two years. “We’re hoping it will be in the clinic in five to 10 years,” he says. “That’s assuming nothing goes wrong.”
It’s a tantalizing prospect. “This represents a potential therapy for those patients who aren’t fortunate enough to get a transplant or aren’t eligible for one,” Badylak says. “It’s a terrific step forward.”