Replacing body parts now more than ‘science fiction’

If Dr. Laura Niklason has her way, vascular surgeons will someday be able to pull human veins off a shelf, whenever they want, to save lives.

Niklason is a pioneer in the science — and art — of tissue-engineered replacement of human body components. Last year, she led a research team that successfully implanted tissue-engineered lungs, cultured in vitro, in adult rats. For short intervals of time, the engineered lungs exchanged oxygen and carbon dioxide similarly to natural lungs.

Now she is turning to the vascular system. Niklason, professor of anesthesiology and biomedical engineering and a member of Yale Medical Group, was senior author of a study published this month in Science Translational Medicine that demonstrated the efficacy of tissue-engineered vascular grafts that are immediately available at the time of surgery, with decreased potential for infection, obstruction or clotting. Niklason oversaw all the research, which included scientists from Duke University, East Carolina University, Yale and Humacyte — a private company focused on human tissue engineering, of which Niklason is a founder.

The Yale Daily Bulletin talked to Niklason recently about her team’s newest research and the burgeoning field of regenerative medicine.

How did you get interested in tissue-engineering?

I got interested in the mid-90s, when I was finishing my clinical training and selecting a research focus. At the time, tissue engineering was either “science fiction” or “lunatic fringe,” depending on whom you spoke with. However, I saw this emerging field as a wonderful opportunity to fuse expertise in medicine, biology, engineering and the physical sciences to create new therapies that might one day impact clinical care.

Were you surprised at how the cells grew on a matrix?

What has surprised and humbled me is the amount of pre-programming that our cells possess. What we are finding in regenerative medicine, over and over, is that we need provide only the approximately correct cues for cell growth, and the cells will respond and recapitulate tissues having amazing complexity.

Your success in implanting functioning lungs in rats garnered worldwide publicity. What was the reaction in the scientific world to your findings?

Some say that 2010 was the “year of the lung.” There are several groups that have reported substantial headway with lung regeneration in the past 12 months. These advancements have triggered enormous interest, both at the level of federal funding and in the private sector. I think we will see substantial resources being devoted to lung cellular therapies in coming years.

What made you turn next to the vascular system?

Actually, my group has been working in arterial tissue engineering for the past 16 years. Indeed, we published the first report of a completely autologous, tissue-engineered artery in 1999. Our recent report in Science Translational Medicine demonstrated that arteries can be engineered from allogeneic [i.e., genetically different] cells, decellularized, and then can be used off-the-shelf for vascular replacement in allogeneic hosts. This means that engineered tissues do not necessarily have to be taken from the patient. In some cases, tissues can be as readily available as other medical devices.

How long do you think it will take before tissue-engineered grafts are a reality for vascular surgeons?

We are hoping to begin clinical trials of the engineered arteries within the next year.

What do you see as the future for regenerative medicine?

I see regenerative medicine as taking multiple paths, all simultaneously. In some cases, for restoration of connective tissues, it may be possible simply to provide extracellular matrix and no cells, as we have shown with the engineered, decellularized arteries. In other cases, such as reconstitution of solid organs such as lung or liver, cells from the recipient will certainly be required. For solid organs, induced pluripotent stem cells will likely provide the cell source for regeneration, either in vitro or in vivo.

What’s next for you, in particular?

I’m having the time of my life! We will continue to focus on bringing regenerative medicine therapies to the clinic, both for the artery and for the lung. It may be that we take up other connective tissues as well, in the near term. The upcoming challenges are enormous, but also very exciting.

— By Helen Dodson