Issue link: https://tmcpulse.uberflip.com/i/1125769
t m c » p u l s e | j u n e 2 0 1 9 t m c » p u l s e | j u n e 2 0 1 9 12 The scaffold is then hooked up to tubes and placed in a bioreactor, where it is infused with nanoparti- cles delivering a special concoction of growth factors—including platelet- rich plasma, fibroblast growth factor 2 (FGF2) and keratinocyte growth factor (KGF)—for 30 days. (The team handmade their first bioreactor in 2013 from a Petco fish tank and nuts and bolts from the local Home Depot hardware store.) The team also reconstituted an immune system in the new bioen- gineered lungs by replenishing it, pre-transplant, with alveolar macro- phages—which clear out infectious and toxic particulates that pollute the respiratory tracts—and infusing it with a serum made up of the pig's blood cells. "As an immunologist, I under- stood that if you just put in a sterile lung, you're going to get an infec- tion," Nichols said. "Without an immune system in the lung as it developed, we don't get past 15 days. You get a fungal contamination overgrowth." Where other researchers tried to transplant bioengineered organs and failed—because the animals suffered complications—Nichols and Cortiellas had four pigs that thrived. The bioengineered lungs developed a fully functioning network of blood vessels and lung tissues without additional infusions of growth factors within two weeks of being transplanted. All of the pigs remained healthy, but were eutha- nized post-transplantation after 10 hours, two weeks, one month and two months, respectively, so the team could assess how well the bio- engineered lungs adapted to their new host environment. While the animals' blood oxygen levels were holding at 100 percent because each pig still had one of its own fully functioning lungs, the bioengineered lungs were not devel- oped enough for the researchers to allow the animals to breathe exclu- sively with the lab-grown organs. 'All of these little pieces' Determining how well animals fare with only bioengineered lungs is the next challenge for Nichols and Cortiella. As a byproduct of all their work with bioengineered organs, the researchers have made interesting and important discoveries that could impact science in a variety of ways. By learning how to revascularize and rebuild the vascular system, for example, they've developed a way to enhance tissue development, which has positive implications for wound healing. "When you look at it that way, all of these little pieces that we've come up with don't just impact what we're doing for bioengineering lungs. They could be used to help in wound healing, other surgeries, transplan- tation and the development of other organs," Cortiella said. But the big question looms: When will they be able to develop a lung to transplant into humans? Even with adequate funding, Nichols said it would take at least five to 10 years before they could produce a lung for compassionate use, a designation by the U.S. Food and Drug Administration that allows patients with immediately life-threatening or serious con- ditions to access investigational treatment. "Although we worked as hard as we could and as fast as we could, there will always be people who hear about our work and say, 'I'm willing to be a guinea pig because I need a lung today.' That's really hard," Nichols said. "I spend weekends and holidays in the lab doing this work. You can never work fast enough … to get it to where it needs to be, but you always have to do it well." It's a commitment Nichols and Cortiella are passing on to the next generation. "We've made big advances within my lifetime. Definitely within my students' lifetime, they'll see clinical application," Cortiella said. "Like a relay race, it's their turn now." 1709 Dryden Road, Houston, TX 77030 westinhoustonmedicalcenter.com