Discussing the Path to a Tissue Engineered Liver

An interesting interview with a tissue engineer can be found at the Methuselah Foundation blog. It covers one view of the path from today's research to the clinical availability of complete engineered livers constructed to order, among other subjects:

[The most significant challenge] definitely has to do with scaling up our cell sources, because the liver is such a large organ, and you just need an enormous volume of cells. We can take fat-derived bone marrow stem cells and turn them into pretty much any cell that we want, but we need such large quantities that we may have to combine cells from different populations in order to get enough. [So] we're going back to how we tackled it for the small bowel, which was to use clusters of cells known as organoid units rather than single cells alone. For the bowel, what that cluster looks like is an epithelial cell - the specialized stem cell of the intestine - with a little ball of cells gathered around it. One of the beauties of these organoid units is that because all of the cells are together, they've already got their natural architecture in place. When you're working with single cells, they have the unfortunate habit of changing into other cells that you don't want. And the more you can keep them together, the happier they are. So these already existing cell architectures turned out to be very useful to us.

Likewise, with the liver, rather than using single cells alone and therefore having to figure out how to mass produce them in order to get enough, we're exploring whether or not we can use these organoid units instead and get them to expand and coalesce into functional tissue. It's kind of like giving the whole process a head start. Instead of saying, "Okay, two cells need to get together and start talking," we're saying, "Can we put 10 cells together and get them to talk to another 10 cells?"

Down the line, we're still going to have to figure out where these cells will come from. With pigs, I can take the liver from one pig and turn it into a scaffold, and then take another pig and break down its liver in order to get a bunch of little organoid units out of it, which I can then seed back into the scaffold. That's great, but it's not clinically translatable. I can't really go to a human patient and just take out little bits of their liver and start chopping them up, because they need their liver to survive. So it's a bit of a Catch-22 at the moment.

In the end, I wonder whether we may have to figure out how to harvest a smaller portion of organoid units from small biopsies of a patient's liver, seed them into a scaffold alongside other stem cells, and then somehow get those organoid units to turn the adjacent stem cells into liver cells. We do have a little bit of lab evidence that this could work, because we've taken bone marrow stem cells, co-cultured them together with epithelial cells from the bronchi, and these stem cells have shown signs of turning into epithelial cells themselves. But this still needs to be explored in a lot more detail.

In general, we'd eventually like to be able to say to you, "Here's a fully seeded new liver, and you can have a full transplant." Before we get to that point, however, it may also be possible to use a partial tissue-engineered liver to make some kind of dialysis machine, much like we do for the kidney. This would give us the opportunity, step by step, to offer an intermediate form of treatment that would give your liver a chance to regenerate a little bit and regain some of its function.

Based on the work we're doing now, I think we'll need another four to five years at least before we're ready to find our first human patient and do a serious pre-clinical GLP study, which is the completely audited study that the regulators would approve of. And that's for the dialysis treatment. Once you got the dialysis up and running, from there it may just be a case of scaling it up to full engineered organ transplants. I don't know how long that will take.

Link: http://mfoundation.org/blog/?p=213

Comments

This is an interesting way to create tissue for liver. I hope it will help speed up creating organs. My desire is that they will start creating via 3D whole organs by 2020, though they have quoted it may be done in 10 years time. The sooner the better in my book:)

Posted by: Robert Church at October 13th, 2014 5:25 PM

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