Signals Blog

image courtesy of John O’Neill, first author

For most areas of medicine, the supply of a treatment can easily meet demand (access issues aside). Need an antibody? A steroid? Millions of pills are manufactured every day.

The case could not be more different for solid organ transplantation, for which the list of patients with end-stage organ failure vastly exceeds the number of organs available for transplant.

If that weren’t bad enough, the situation is even worse for patients with lung disease, because only 1/5 lungs from consented donors meet current transplant criteria.

Biomedical engineers have responded by trying to engineer whole lungs de novo, you know, the type of thing you imagine seeing in science fiction movies, which is portrayed as both fascinating and terrifying at the same time (why terrifying? What confidence does this instill in science ethics?).

But as you might guess, recreating human development to create a hierarchically organized, multicellular organ, with every cell in its rightful place, is kind of hard.

It turns out that there is a solution, and it’s really quite feasible. It’s based on the fact that within the 80 percent of lungs that are not suitable for transplant, a fraction only marginally miss.

This has inspired transplant surgeon Dr. Matthew Bacchetta and John O’Neill, and collaborating engineers at Columbia University/New York Presbyterian Hospital to attempt a method at refurbishing these lungs so that they are transplant ready.

Their strategy, published in the most recent issue of Nature Biomedical Engineering, is based on a somewhat radical modification to ex vivo lung perfusion (EVLP). Currently, EVLP machines can extend the lifespan of donor lungs by about six hours, but eventually lung quality diminishes due to the build-up of waste products that are not cleared, because the lung is not connected to other important organs such as the liver and kidney.

Rather than building a fancier EVLP machine, which somehow filters all these waste products, Dr. Bacchetta et al. thought, “why not use a readily available natural bioreactor, which is perfectly suited to do this?” In other words: let’s hook this EVLP circuit up to a real patient and let them clean up the donor lung’s metabolic waste while it recovers to transplant quality.

Of course, this method of “cross-circulation” was not initially tested in humans, yet the investigators showed some pretty staggering results. By hooking a healthy ex vivo pig lung up to another living pig (the “recipient”), the donor lung exceeded transplant criteria even three days out, demonstrating enhanced survival capacity. However, lungs could also be revived, as lungs initially exposed to some minor damage recovered by the end of three days on cross-circulation.

What’s cool is that this method also opens the door to many types of donor lung modifications, for which the investigators show some proof-of-concept data. For example, while it would be difficult to target stem cells to a lung within a body (and require an enormous number of cells), having the lung survive for several days in relative isolation makes it accessible to such regenerative treatments. Just imagine all the possibilities!

I have been lucky enough to witness this process in person, and it is truly surreal. But in a way, it is also very familiar. In many areas of life, if there is a machine part that is broken, we take it out, fix it, and make it useable again. The fact that transplant surgeons might be able to give ‘almost-useable’ donor lungs a bit of a polish to make them functional again is an incredible boon to a population of patients waiting for better solutions.




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Holly Wobma

Holly Wobma

MD/PhD student at Columbia University
Holly is an MD-PhD student at Columbia University in New York. She recently (2011) completed a Bachelor of Health Sciences Honours Degree from the University of Calgary, where she pursued research related to nanotechnology and regenerative medicine. In addition to research, she enjoys participating in science outreach roles. Previously, she contributed to an award-winning Nanoscience animation produced by the Science Alberta Foundation (“Do You Know What Nano Means?”), and served on the board of directors for the Canadian Institute for Photonic Innovations Student Network. Holly's lab tweets @GVNlab.