Growing blood vessels and lungs in the lab

Laura Niklason first came up with the idea of growing human blood vessels while she was doing her residency at Massachusetts General Hospital in the 1990s.

A patient was undergoing a heart bypass—a surgery in which a physician takes a blood vessel from another part of the patient’s body and then sews it on top of a clogged vessel, forming a bypass around the blockage. The problem, in this instance, was that doctors could not find a suitable replacement vessel in either the patient’s legs or arms, so they had to go into his abdomen to find one—not an ideal choice.

“That was eye-opening for me,” said Niklason (BS, ‘83, physics; BA, ‘83, biophysics).

With the goal of providing a ready supply of vessels, she created a prototype engineered blood vessel in 1997, and in 2012 an advanced version was used successfully in the first human patient. The FDA has fast-tracked the engineered blood vessel, moving it into Phase 3 human clinical trials. Meanwhile, she has also begun work on finding ways to grow new lungs for transplantation.

For this groundbreaking work in tissue engineering, Niklason is a 2016 LAS Alumni Achievement Award winner.

Niklason, a professor of anesthesia and biomedical engineering at Yale University, grew up in the south suburbs of Chicago and says she was probably seven or eight years old when she decided to become a doctor.

“I wanted to be the person who saves the day, I guess,” she recalled.

Niklason skipped a couple of years of school, so when she arrived on the University of Illinois campus in 1979, she was only 16 years old. However, she said, “I didn’t feel that much younger than other people.”

As a 16-year-old physics major, she may have been an atypical student, but the advantage of a large school was that it was diverse enough that she could find a peer group of like-minded budding scientists.

After graduating from Illinois in 1983, Niklason went through a combined PhD/MD program at the University of Chicago, but finished her MD at the University of Michigan where her future husband was on faculty.

During the third year of her anesthesia residency in 1995, she joined the laboratory of Robert Langer at MIT—another major turning point in her career. As she says, “At the time, his lab was one of the few in the country that was exploring this new world of tissue engineering.”

It was while she was working in Langer’s lab and doing her anesthesia training that she decided, “I am going to grow a blood vessel. At the time, it was a fantastical idea. Even my best friends thought it was kind of funny. But I didn’t know any better, so I started working.”

Once the vessel prototypes were developed, she decided that for the first clinical application they would target patients who undergo dialysis three times a week. In preparation for dialysis, doctors sew a replacement blood vessel just under the skin. Blood is drawn out through this replacement vessel, and the dialysis machine then cleans the blood, which is returned to the patient’s body through the same vessel.

Because replacement vessels are used so heavily in dialysis and are subject to failure, they are often made out of Teflon. But Teflon blood vessels are much more susceptible to infection, which is why Niklason’s team wanted to replace them with bioengineered vessels that are, basically, human tissue. To grow the new blood vessels, Niklason and collaborators place human vascular cells on a vessel-shaped scaffold, and then the tissue grows into the shape of a vessel inside of a specialized bioreactor. 

After developing their first successful blood vessel in the lab in 1997, her lab spent the next 15 years refining the technology. This culminated in the first patients being implanted with the laboratory-grown vessels in 2012. Three and a half years later, the first two dialysis patients are still successfully using the same replacement vessels grown using Niklason’s technology.

In all, a total of 60 dialysis patients in the United States and Europe have now received the engineered blood vessels, and an additional 175 patients will receive the vessels as part of the Phase 3 clinical trials. The vessel has proven to be mechanically strong, significantly lowering both the failure rate and infection rate.

Building on the success of engineered blood vessels, Niklason has also turned her eyes to growing new lungs in the laboratory.

During her training as an anesthesiologist, Niklason specialized in intensive care unit medicine, and she worked with many patients with organ failure, including lung patients who are on ventilators because they cannot breathe on their own.

“There are a few tissues in the body that don’t repair themselves very well after they have been injured, and lung tissue is one of them,” she says. What’s more, lung transplantation does not have a high success rate, so her idea is to grow new lungs in the lab.

Lungs are mostly air, but they are made up of air sacs, and the surface area of these sacs is about as big as a tennis court. “So you might say we’ve got a tennis court inside our chests,” she said.

To grow this vital organ, Niklason’s team washes cells out of a lung—in this case the lung of an animal. Then they take the remaining protein scaffold and repopulate it with lung cells taken from the patient. This research is in the early stages, but it shows great promise.

In the meantime, Niklason started a company, Humacyte, in 2004, to move the engineered blood vessels forward. She has partnered with AlloSource, a tissue procurement organization run by Tom Cycyota, a 1980 LAS alumnus in biology who received the LAS Alumni Humanitarian Award last year. (Niklason didn’t know about the Illinois connection until after they started talking about collaborating.)

With engineered blood vessels showing so much success for dialysis patients, Niklason sees many other possible uses for replacing tubular tissues in the body, such as the windpipe or esophagus in cancer patients.

When Niklason started this work in the 1990s, she says, “There was a tremendous amount of irrational exuberance about tissue engineering. People were saying we’re going to grow a new arm in 10 years, and it’s all going to be fabulous.”

When that didn’t happen, the 2000s saw a wave of pessimism, but work such as Niklason’s has ushered in a new period of cautious optimism.

As she put it, “We are on the cusp of what I think is going to be a permanent change in medicine.”