New lab-grown lungs

Two new lab-grown versions of lungs may one day serve as a way to sidestep both animal testing and organ transplantation.

Image: Wikimedia commons,
Patrick J. Lynch

One engineered rat lung, described in Science Express today (June 24), even successfully helped rats breathe for brief periods. "This is the first ever published paper that really demonstrates that regenerative medicine can provide an alternative to clinical transplantation of the lungs," said translational medical researcher Paolo Macchiarini of linkurl:Karolinska Institutet;http://ki.se/ in Sweden, who was not involved in the research. Currently, the only treatment for the lung diseases that cause some 400,000 deaths each year is to transplant a new, healthy organ -- a procedure that is hampered by organ rejection complications and a severe shortage of donors. But now, bioengineer and vascular biologist linkurl:Laura Niklason;http://www.seas.yale.edu/faculty-detail.php?id=79 of Yale University and her colleagues may have developed a way to eventually address both of these issues. Treating adult rat lungs with detergent solutions to remove their cellular components gave the researchers their starting point -- a lung skeleton, or the extracellular matrix that gives the lungs their structure. The team then repopulated the lungs with epithelial and endothelial cells from rat lungs, which grew over the scaffolds to create brand new lungs. The researchers then implanted the new lungs into rats for up to two hours, during which time they found evidence that the engineered lungs were successfully participating in gas exchange. However, they also started to see some blood clots form in the vasculature of the lungs, as well as small amounts of leakage of blood into the airways, which most likely stemmed from an imperfect matrix and incomplete covering of new cells, Niklason said. "Clearly we're close, but not all the way there yet," she said. "We really view this work as laying a scientific and technological basis for regenerating lungs in the long term." Still, Macchiarini said, this is an important step. "The door is open now in the sense that we now have the tools to investigate how tissue engineering can generate lungs." The end goal, which may still be a couple of decades away, Niklason said, is to use a patient's own cells to build an implantable lung, eliminating the potential rejection problems that come along with organ transplantation. This procedure would also broaden the potential pool of scaffold donors to include cadaveric organ donors and even large animals, she added. Meanwhile, at the linkurl:Wyss Institute for Biologically Inspired Engineering;http://wyss.harvard.edu/ at Harvard University, researchers have created a different kind of laboratory-built lung -- something they call a lung-on-a-chip. The device, devised by cell biologist linkurl:Don Ingber;http://wyss.harvard.edu/viewpage/121/donald-e-ingber and his colleagues and published in this week's Science, is an engineered lung of sorts, but not for implantation into a living organism. Instead, it is a microchip intended to be used as an in vitro model system for testing drugs or the toxic effects of any variety of substances without the use of animal models. "Any American knows that drugs are incredibly expensive and take a long time to get to patients, and a large part of that is animal costs," Ingber said. "The idea of having quick screens or being able to do massive throughput analysis [for toxins] is exciting." The chip is constructed of a porous, flexible polymer, on which human epithelial and endothelial cells are cultured, much like Niklason's engineered rat lungs. The cells are then subjected to a lung-like environment, both in terms of their exposure to air on one side and fluid on the other, as well as the mechanical stretching that results from normal breathing, "recapitulating organ-level function" on a small, manageable chip, Ingber said. Plus, because the polymers on which the lung cells are cultured are clear, Ingber added, it is possible to do high resolution imaging of the tissue's interactions with the drug or toxin being tested, as opposed to in an animal, where "it's really hard to see what's going on." "You had everything that you would in vivo except that here you have it externally," said tissue engineer and anesthesiologist linkurl:Joaquin Cortiella;http://anesthesia.utmb.edu/faculty/bios/Cortiella.html of the University of Texas Medical Branch in Galveston, who did not participate in either study. "It's a way to test anything from pathogens to toxic things to drug studies." "This paper [is] a major advance for evaluating toxicological methods, [as well as] pharmacological studies [and] nanomedicine," agreed Macchiarini. However, he added, it will not replace animal studies altogether. "In your body, you have thousands of reactions at once. We need to take into account." "It's going to be a long time before you replace animal models," Ingber agreed, "but it's the first step towards building in that direction -- we're able to recapitulate complex functions." In fact, Ingber and his colleagues are already working on building a more comprehensive testing tool. By using vasculature networks to connect forthcoming chips that represent other organ systems, such as the gut, heart, liver, and bone marrow, Ingber and his colleagues might one day be able to achieve their "long range goal of human-on-a-chip," he said. "Who would have thought 15 years ago the microchip industry would lead in this direction?" Ingber wondered. "It's a great of example of where engineering, biology, and medicine are beginning to merge." T.H. Peterson, et al., "Tissue engineered lungs for in vivo implantation," Science Express, June 2010. D. Huh, et al., "Reconstituting organ-level lung functions on a chip," Science, 328:1662-8, 2010.
**__Related stories:__***linkurl:New Smoking Gun?;http://www.the-scientist.com/article/display/57240/
[April 2010]*linkurl:A single pathway for lung damage;http://www.the-scientist.com/blog/display/54558/
[17th April 2008]*linkurl:Betting on Better Organs;http://www.the-scientist.com/article/display/53878/
[December 2007]

New lab-grown lungs

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