In the beginning, there was the earmouse: naked, pink, and toting on its back a grotesque ear-like appendage the size of a child’s ear. When an image of this mouse-grown “ear”— actually a piece of cartilage taken from a cow’s knee and implanted into the rodent—circulated on the Internet, it shocked scientists and the public alike. But it also suggested the potential for tissue engineering to revolutionize the options for those who needed organs or body parts—in this case, an ear.
Unfortunately, science doesn’t always move in smooth leaps and bounds. And so, 20 years later, political and bureaucratic hurdles have meant that genetically engineered ears still aren’t commercially available in the U.S., where hundreds of thousands of people have suffered ear injuries due to gunshot wounds, cancer of the ear or microtia, a malformation of the external ear. (In China, the researchers who developed the earmouse are currently testing the technique of growing cartilage into ears on human patients.)
Now, a team of researchers from the U.S. and U.K. are aiming to change that. Inspired by the earmouse, doctors at the University of California at Los Angeles and the University of Edinburgh's Centre for Regenerative Medicine have perfected a new technique to grow a fully formed human ear, using patients' own stem cells. They begin with a 3D-printed polymer mold of an ear, which is then implanted with stem cells drawn from fat. As these stem cells differentiate into cartilage, the polymer scaffold degrades, leaving a full “ear” made of mature cartilage cells.
The new approach could “change all aspects of surgical care,” says Dr. Ken Stewart, one of the researchers and a plastic surgeon at the Royal Hospital for Sick Children.
The researchers focus on children with microtia, a congenital deformity that causes patients’ ears to underdevelop. The condition leaves people with a hooked piece of cartilage and skin on one or both sides of their head, along with a host of hearing issues. Currently, if a microtia patient needs a new ear, a surgeon must go into their body and borrow cartilage from the rib. The surgeon then carves that cartilage into the shape of the ear, puts it under the skin on the side of the patient’s head and grafts more skin on top. The method is risky and complex, and doesn’t create an ear that truly feels a part of the patient.
For the new technique, Stewart uses an Artec 3D scanner to create a digital model of the patient’s unaffected ear so that it can be printed. (If the microtia patient has two affected ears, then Stewart will use a family member’s ear as a model.) The model is made of particular synthetic polymers that the researchers have found are attractive to stem cells—that is, that stem cells tend to latch on to. His colleagues, tissue regeneration expert Bruno Péault and clinical lecturer in plastic surgery Chris West, then inject the 3D-printed model with the stem cells, which are purified from the patient’s tissue using a cell sorter.
Key to this process is the fact that the stem cells are derived from fat. First, extracting stem cells is far less invasive than performing a bone marrow extraction. But fat also contains the best kind of stem cells for this kind of process, because they’re plentiful and easy to extract, as the researchers demonstrated in a paper published last March in the journal Stem Cell Research & Therapy. Moreover, fat tissue contains mesenchymal stem cells: powerful stem cells that have the ability to grow into new bone, cartilage, muscles and fat.
The researchers emphasize that this technology has the potential to go far beyond microtia. It’s also applicable to patients who have lost an ear to cancer, or who need other body parts made of cartilage—a new nose, new knee joints or hip joints, for instance. It would even be conducive to patients who may need more fat; say, if they were shot in the face and lost a good chunk of their cheekbone.
So why has it taken this long?
Stem cell research in the U.S., particularly that involving embryonic stem cells, has long drawn ire from conservative and religious groups. Federal funding for embryonic stem cell research was greatly restricted under the second Bush administration in 2001. Although President Obama later overturned Bush’s presidential order and opened the doors for more stem cell research in 2009, vestigial restrictions remain. Blanket guidelines thrown over all study in the U.S. have “hampered some stem cell research in America, to a certain degree,” according to West of the University of Edinburgh.
In other words, even research involving adult stem cells—like the mesenchymal stem cells West’s team is using—tend to get lumped in with that controversy. “The conservative side of society doesn’t want anything to do with embryonic stem cell research and unfortunately, they’ve thrown the baby out with the bathwater,” West says. “Because there’s been such an opposition to stem cell research, it’s put a halt on a much broader research area than just embryonic stem cells.”
In the U.K., the researchers must apply for ethical approval from an independent panel of experts and laypeople, who scrutinize the proposal at a level that other types of research don’t require. China, by contrast, is known for having one of the most unrestricted stem cell oversight policies in the world. “[China] is very relaxed when it comes to clinical trials and investigations in humans and stem cells,” says Péault, of the University of Edinburgh and the University of California. “Their regulations are certainly much more relaxed than ours.”
“They’ve had a head start,” says West. “That’s not to say they have done anything wrong, it just means we have to take a longer route to get to the same point.”
Péault attributes the slow acceptance and public release of this technology to old-world outlooks on medicine, and the novel nature of the new technique. “It’s a very special project. There’s almost something artistic in this project,” he adds, noting that Stewart carves most of the ears he creates by hand. Yet although the team is still working with the FDA to get approval to work with human patients, Péault still hopes they can complete this tech and apply it to patients within a matter of months.
“Ideally, my colleagues will be able to use this," he says. "I am very interested in the actual medical impact it will have.”
Editor's note, January 3, 2017: This article originally stated that the Artec 3D scanner was used to print the ear model; it is actually used to scan the patient's ear.