Your organs are a lot of things—a powerful computer (in the case of your brain), detoxers (your liver and kidneys), breathing devices (your lungs). But there’s one thing they’re decidedly not: transparent.
That’s unless you’re Kevin Bacon in The Invisible Man, or if your organs end up in the lab of Ali Ertürk, director of Helmholtz Munich’s Institute for Tissue Engineering and Regenerative Medicine. Writing in the journal Cell, Ertürk and his colleagues detail how they’ve treated human organs to make them see-through. Next, by adding special dyes to the now-transparent organs, they can map kidneys, eyes, and brains on a cellular level, which could one day help scientists 3D-print versions of them.
You don’t have to turn a brain transparent to see inside it, of course. An MRI can image the insides of a brain in detail, and a functional MRI (fMRI) measures brain activity by looking at blood flow. But to get at what’s happening on a cellular level, normally you would have to section the brain, damaging it as you cut into it. The beauty of this new technique is that the researchers can keep a transparent organ entirely intact while still peering deep inside it, seeing right down to the cellular level. They can image networks of teeny-tiny blood vessels, undisturbed in their natural arrangement. For example, in the kidneys, they can see tufts of fine capillaries known as glomeruli structures, which help filter urine.
You may have already seen Ertürk’s previous work making mice transparent to study how they respond to injury. (Dead mice, to be clear.) Working with human organs, though, the team ran into a problem: stiffness. The mice they used in the earlier experiment were only a few months old, so their tissues were nice and soft, allowing chemicals to penetrate them. The human organs they had to work with were from much older individuals, and they had accumulated gobs of stiff molecules like collagen over the years—a perfectly natural fact of life, by the way.
“We had to somehow find a way to relax this stiffness,” says Ertürk. The solution—in more than one sense of the word—was a “zwitterionic” detergent (read: not available in your average drug store) called CHAPS, “which could penetrate through these stiff molecules and form small channels that would then allow the passage of the solution.”
The team could then dehydrate the organ with alcohol and remove the lipids, or fats, by using the solvent dichloromethane (which is also used to decaffeinate coffee). Because this process entails removing so much material, each organ was also pretreated with paraformaldehyde so it wouldn’t decompose, collapsing in on itself during the process. “So everything is fixed in time and space,” says Ertürk.
With its fat and water gone, the organ was now transparent. Which is cool and all, but not particularly useful on its own. To really map out the structure of the organ, the team had to add dyes to illuminate structures like capillaries in 3D. The dyes can get deep down into the organ because the CHAPS detergent has already dug those small channels throughout. They used a special fluorescent dye that, based on its chemistry, would be attracted to a certain part of the organ—say, the walls of vessels—and stick there. Then, scanning the organ with a laser microscope, the researchers could illuminate in fine detail the organ’s complex structures.
The resulting cellular 3D maps are extraordinarily beautiful but potentially also useful for one day 3D-printing organs. “So we know, mathematically, what does it mean to become a kidney?” says Ertürk. “We have a formula that we could use to build up back the whole kidney. So that's a major dream that we are pushing for.”
That would be a dream for many, many people around the world: In the US alone, more than 100,000 people at any given time are waiting for an organ donor, and 20 die each day because an organ never came through. The promise of 3D printed organs is to make them more readily available and to avoid complications from a person-to-person transplant, like the recipient’s body rejecting a transplanted organ.
A major challenge of growing organs in the lab, though, is vascularization, or providing all parts of the organ with the blood it needs to survive. This new technique for transparent organs just happens to map every bit of a kidney, showing how the organ is vascularized as it would be in the human body. And that might help create 3D-printed organs that will have the vascular network and blood supply needed to survive in a real human body.
Up until this point, imaging an organ has been a painstaking and fairly disruptive process. One technique is to cut super-thin slices of an organ, take an image of each slice, and stack those images to rebuild the structure. “But you can imagine that when you cut, you're actually disrupting the structure,” says Rice University bioengineer Jordan Miller, who wasn’t involved in this new work. “And then if you julienne fries, putting those fries back together again is really hard to do.” In particular, it’s difficult to perfectly align those slices to get an accurate reconstruction of the organ.
What Miller and others are working toward is a better understanding of the wildly complex structure of organs, so as to replicate that intricacy in artificial organs. After all, if you copy the structure, you might get the same function. “There are no structures in the known universe as complicated as the ones we have inside of our body,” says Miller. “So it's just an incredible challenge. And we really need technologies like this that will get us more information about how our bodies are composed.”
Here’s to transparency, then.