The procedure brings scientists closer to one day providing bioengineered lungs for humans
Jean Niles, Joaquin Cortiella and Joan Nichols
For the first time, researchers have created lungs in the lab and successfully transplanted them into pigs.
These bioengineered lungs, described online August 1 in Science Translational Medicine, developed healthy blood vessels that allowed pigs to live for several weeks after surgery without medical complications. That’s a significant improvement from previous efforts: Lab-grown lungs implanted in rodents failed within hours, before the lungs could develop the complex blood vessel network necessary for long-term survival.
If the new procedure can be adapted for humans, with bioengineered lungs grown from a patient’s own cells, that could reduce the risk of organ rejection and slash wait times for organ transplants. In the United States, where about 1,500 people currently are on a waiting list for a lung transplant, the average wait is a few months.
“This study really brings the whole research field to the next level,” says Xi “Charlie” Ren, a biomedical engineer at Carnegie Mellon University in Pittsburgh not involved in the work.
For the study, immunologist Joan Nichols at the University of Texas Medical Branch at Galveston and colleagues built lungs for four pigs by first using a sugar and detergent mixture to strip the cells from lungs of donor pigs. That left sterilized, pearly white, lung-shaped scaffolds made of the intercellular proteins. (In humans, researchers envision using donated organs or 3-D printing made-to-fit lung scaffolding.) The researchers then repopulated each scaffold with blood vessel and lung tissue cells from the pig destined to receive that organ.
Each engineered lung grew for 30 days inside a bioreactor tank, pumped full of nutrient cocktails that helped cells stick to the scaffold and multiply in the right spots. The researchers then replaced the left lung of each pig with the bioengineered version.
After surgery, Nichols’ team allowed one pig to survive for 10 hours, another for two weeks, a third for a month and the fourth for two months. At each pig’s demise, the researchers did an autopsy on the animal to see how the new lungs integrated into the pigs’ bodies over time. None of the animals was given immunosuppressant drugs, and none of the transplants was rejected. Inside a pig’s body, the bioengineered lung’s blood vessels plugged into to the animal’s natural circulatory system, supplying the organ with oxygen and nutrients to survive.
The animals’ post-op recovery was “pretty amazing,” Ren says. The pig that lived two months after surgery didn’t experience any breathing problems, and its lung transplant was colonized by bacteria that inhabit normal pig lungs — signs that the tissue was developing normally and integrating well into the body.
But these lab-grown lungs aren’t quite ready for prime time, says Laura Niklason, a biomedical engineer at Yale University not involved in the work. While the bioengineered lungs linked up with the pigs’ circulatory systems, the organs weren’t connected with the animals’ pulmonary arteries — which carry low-oxygen blood for the lungs to replenish with oxygen from air breathed in. That left the pigs to rely on their natural right lungs for air after surgery.
“The next step is hooking the organ up to the pulmonary artery” to ensure that bioengineered lungs get oxygen into the blood as well as normal lungs, Niklason says.
J.E. Nichols et al. Production and transplantation of bioengineered lung into a large-animal model. Science Translational Medicine. Published online August 1, 2018. doi: 10.1126/scitranslmed.aao3926.
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