The first viable prototype of an artificial lung offers new hope for the more than one thousand people awaiting lung transplants across the United States.
The first viable prototype of an artificial lung offers new hope for the more than one thousand people awaiting lung transplants across the United States. Organs are currently matched based on blood and tissue type and a variety of other measures, and many patients die before finding an appropriate donor organ. Bioengineered lungs could offer new options for those patients.
“Other labs have tried to do it—and we’ve tried and failed many times. It turns out that it’s really complicated to do,” says Joan Nichols, associate director of the Galveston National Laboratory at the University of Texas Medical Branch, whose team spent the last 15 years developing the prototype. “To succeed, we really had to change our view of what we were doing.”
That change led to a remarkable success: Nichols and colleagues at UTMB have successfully developed bioengineered lungs and transplanted them into living adult pigs. The researchers kept the pigs alive for up to two months and found no signs of transplant rejection. The results were published in the August 2018 issue of Science Translational Medicine.
Nichols credits a paradigm shift in their engineering process to creating viable lungs.
“We figured out that we had to build the microvasculature first, those tiny blood vessels and capillaries you need to have for gas exchange to happen [when organs breath],” she says. “At first, we thought we could make the lung first and then add in the vascular system later. But we had to create the lung’s vascular system first and then build the rest of the lung around it.”
Nichols and colleagues started with a support scaffold created from a healthy pig’s lung. The lung was treated using a solution of sugars and detergent to clean out any blood and cells, leaving only the structural proteins, or “skeleton,” of the lung behind.
“This scaffold has the trachea, the branching airways—that’s what’s left behind as well as the branching vascular components,” she says. “Then we place nanoparticles and hydrogels in the right places so when we put the cells back in we had lots of growth factors right at the point we wanted to rebuild those capillaries and blood vessels.”
The structural proteins of the scaffold, however, do not provoke significant immune responses when transplanted. To overcome that, the researchers placed the scaffold into a tank where they slowly added growth factors, stem cells from the intended transplant recipient (which reduce the likelihood of rejection caused by “alien” cells), and other critical nutrients before being placed in a bioreactor for 30 days. The lab’s previous failures, as well as complex modeling techniques, allowed the team to learn now to fill in the blanks of the organ using stem cells, nanoparticles, and hydrogels.
“It’s a stepwise process,” she says. “It didn’t just happen. It happened slowly over time, giving us the information we needed to make the lung develop properly. You can get a cell. You can put it in a general location, but you can’t make it do what you like without help. You have to entice the cells with these growth factors slowly at exactly the right time so they can rebuild those tiny vascular bits that will support blood vessel development.”
Upon completion, the bioengineered lungs were transplanted into four pigs. There was no indication of transplant rejection when the animals were examined 10 hours, two weeks, one month, and two months after transplant. The researchers also observed that the bioengineered lungs became vascularized, establishing the necessary blood vessel networks to do its job.
Nichols is pleased with the results from this study, but says there’s still much work to be done. The researchers plan to do a follow-up study to see whether these bioengineered lungs are able to provide ample oxygenation after transplantation.
“We didn’t look at how well the lungs were working in this study,” she explains. “So we want to do the transplants just as we did in this pilot study and then send the pigs back to the farm for 6 months to a year. Then we can bring them back to the lab and stop their normal lung from breathing. That will tell us whether the animals can get enough oxygen and survive just on the bioengineered lung.”
But, for now, Nichols says that 15 years of hard work has helped them find a best—and likely clinically relevant—path forward.
“We learned so much from this study. We know what we’re doing right, what we’ve done wrong, and how to make it so much better,” she says. “This isn’t the kind of science that can go to the clinic tomorrow. But this step-by-step work has gotten us here, the beginning of the preclinical studies that will hopefully lead us to being able to offer bioengineered lungs to transplant patients in the future.”
Kayt Sukel is an independent technology writer.
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