Scientists grow lungs in a lab

07 August 2018

Interview with

Joan Nichols, University of Texas Medical Branch

Lung Diagram

Lung Diagram

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Thousands of people die every year on transplant waiting lists. There just aren’t enough donor organs to meet the demand. Which is why the announcement this week, by scientists in the US, that they’ve managed to grow - in a culture vessel called a bioreactor - new human-sized lungs that can be implanted successfully into pigs, is a huge step forward. Joan Nichols is at the University of Texas Medical Branch at Galveston…

Joan - There are never enough donor organs for people who need to have a lung transplant and that’s people with severe lung disease who we can’t do anything for. People that do go onto transplant lists have long waits for organs and many people even die before they ever receive an organ, and that’s been an issue overall in transplantation since the process began.

Chris - So the issue is one of organ shortage? We just don’t have enough donor organs so what can we do to surmount that?

Joan - One of the ways that we have talked about in my research team is finding a way to make lungs for somebody who needs them. And right now that means using lungs that are discarded, that can’t be used for transplantation and finding another use for them, as either a source for cells to create a new lung, to bioengineer a new lung or as a source of a scaffold, and that’s the other part of this process that we need. We need both a source of cells and a source of a lung scaffold, and we’ve developed procedures to produce scaffolds from lungs that can’t be used for transplantation themselves.

Chris - So that’s the aspiration; that’s the goal where we want to be. We can grow someone a bespoke lung, or at least a lung that’s going to be compatible with them and we can overcome some of these shortcomings of the present situation. What have you got to do in order to make that possible?

Joan - I would start by making a human scaffold, by taking a lung that’s been very damaged and has no live cells left in it. Treat it with a special solution that removes all of the cells but leaves behind the proteins that are the structural support proteins that give it the strength and elasticity that a lung needs to have.

Second step is we take another lung. Again, not suitable for transplantation but has live cells in it this time and remove the cells from all the parts of the lung that make it a lung. And then we prepare to put them together to produce a new lung.

Chris - So you, in summary, get the donor lung; get rid of all the cells just leaving behind this protein scaffolding, which is going to show the cells which is going to be incoming where they need to go; put it into this bioreactor which contains nutrient solution - I presume you’ve got a supply of oxygen there to keep these cells alive and to feed them and then you just slowly add the cells onto this scaffold in order to encourage the right cells to take up residence at the right place?

Joan - That’s exactly what we do. And on a regular basis we add in cells or factors that help support this. Just like a recipe for making a cake, every time we did this for the study we did it exactly the same way to prove that using these procedures we could consistently develop tissues that were lung tissue.

Chris - How long does it take to grow a whole lung of the sort of size a person would need?

Joan - It takes roughly 30 days at this time to produce something that’s still immature, that will continue to develop once it’s transplanted.

Chris - What animals have you done this on, because people have tried to grow lungs in a dish for small animals in the past?

Joan - Those studies with small animals were critical to what we’re doing now. We’ve done it in a large animal model; we’ve done it in pigs. And, by the way, we’re giving the animal one bioengineered lung; they still have one lung that they can survive on that’s there own natural or native lung.

Chris - How many pigs have you looked at and what happened to them?

Joan - Of the four pigs in the study that received bioengineered lungs, they all survived for the length of time that we had wanted them to, so that’s ten hours, two weeks, one month, or two months.

Chris - Does it work? Does the lung actually appear to be exchanging oxygen and carbon dioxide as it should do?

Joan - That’s a huge step, so let’s start with a small step. The tissues survived. The animals didn’t show any respiratory distress or have any fluid development in the lungs or any problems associated with it. The part about oxygenation is a little bit harder because the way that we did this process we were not going to be able to see gas exchange.

But in our next pilot study we will actually go for a long term survival of animals where we bring them back after being back in the farm for maybe a year. We block off their ability to breath from their native lung and we let them breathe on the bioengineered lung alone.

Chris - If the lung is continuing to grow when it goes into the recipient, does this mean then that you could take say a child with cystic fibrosis - a chronic lung condition because of a genetic problem - fix that condition in the new lung that you give them, and then that lung would grow with them?

Joan - That’s what our hopes are. Even before dealing with something like cystic fibrosis, looking for a compassionate use, which just means that somebody cannot survive unless we provided them with this therapy. Perhaps a child that has something called Diaphragmatic Hernia, where the diaphragm doesn’t develop and that blocks development of the lung. These babies cannot survive without some intervention and that’s what we’re looking at in terms of first use for this kind of procedure.

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