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Going with the flow

Building replacements for arteries and lungs takes ingenuity—and patience

Laura Niklason
Photo by Terry Dagradi
Seeing many patients die of organ failure as a physician-in-training and in her work as an anesthesiologist inspired Laura Niklason to make a difference. Though she was initially skeptical that artificial organs would ever be clinically practical, she went on to become a leading figure in tissue engineering, and her “off-the-shelf” arteries, decades in the making, are soon to be tested in human clinical trials.

Having already earned a doctorate in biophysics at the University of Chicago, Laura E. Niklason, M.D., Ph.D., knew when she started medical school at the University of Michigan that research would be a major part of her career. At Michigan, she did work for a local company on ventricular assist devices—implantable machines that help failing hearts pump blood—but after seeing many patients in intensive care die of organ failure, she was skeptical that artificial solutions would ever work for patients over the long term.

But Niklason, professor of anesthesiology and of biomedical engineering, “stumbled into tissue engineering” during her anesthesiology residency at Massachusetts General Hospital. A tutor working in the MIT lab of biomedical engineering maven Robert Langer, Ph.D., showed her a picture of a rat skull in which he had drilled two holes and then permanently repaired one hole by filling it with engineered cartilage. “That made me sit up because it never had occurred to me that it might be possible to reconstitute a whole tissue just from cells,” she says.

In 1995, while still a resident, Niklason found herself working in Langer’s lab as well, now thinking that “this tissue engineering stuff might be the coolest thing ever.” And though she had no previous experience as a bench biologist, she set out to engineer an artery from scratch, spending three years designing scaffolding on which to grow the tissue, creating a mechanical environment for the cells to grow in that mimicked the action of the heart, and concocting a nutrient medium matching the body’s chemical environment.

She continued that work at Duke University, where she moved in 1998. At first, “there were lots of snafus, and lots of burst pipes and leaky fluids,” she says. But in 1999, her team published a paper in Science on the first successful transplant of engineered arteries built from an animal’s own cells. Next she focused on translating the method for human cells and making the process clinically feasible—it took three months to grow an artery, far too long to “ask a patient to hold his breath,” she says.

The solution was to grow arteries from donor cells, and then, in the final step, wash the cells away, leaving only the “skeleton” called the extracellular matrix (ECM). Surprisingly, the tissue didn’t look any different and was just as mechanically strong as cellularized tissue, says Niklason, who joined Yale’s faculty in 2006. “The advantage is that since the cells are gone, there’s no rejection. Because it’s non-living we can store it for months, so we have a tissue that’s off the shelf.” Later this year, Durham, N.C.-based Humacyte, a biotech company Niklason founded while at Duke, will begin its first clinical trials of these arteries, which will be implanted into the arms of individuals with kidney disease to provide a source of high blood flow to expedite dialysis.

Other researchers in her lab are working on lung regeneration as an alternative to lung transplantation, a difficult procedure with a low 10-year survival rate due to infection and organ rejection. The approach is similar to artery engineering: create decellularized lungs, keeping their complex branched vasculature intact, and then seed the ECM with a patient’s own cells.

With a patience that comes from long experience in medical research, Niklason says it may be 20 years before people will be breathing through regenerated lungs. But she’ll keep busy in the meantime. “I’ve piled a lot on my plate, she says, laughing, “but I’ve been doing it for decades.”