Discover article - Wyss Institute at Harvard

Wyss bioengineer Kit Parker (left, with Harvard graduate student Borna Dabiri) is studying howpressure waves from explosive blasts affect brain tissue.James Niemi, lead senior staff engineer at theWyss Institute, demonstrates James Collins’sConcussion in Miniaturevibrating shoe insoles, which help people withbalance and walking problems.Bioengineer Kit Parker, a major in the U.S. Army, was on duty in Afghanistan in 2009 when anexplosive struck the lead vehicle in his convoy. The driver and vehicle commander sufferedmajor concussions in the crash. Their behavior suggested the soldiers had suffered traumatic top, Ingber picks up a pair of oversize shoebrain injuries, or TBIs, which can have devastating long-term effects, including cognitive and insoles wired to small battery packs. HeThe psychiatric Wyss Institute’s disorders, suite seizures, of machining and early-onset tools Alzheimer’s disease. “I thought to myself,explains that elderly people often sufferincludes ‘There’s 3-D no printers first aid (one for this,’ of which ” Parker is shown says. at If the men had suffered a broken limb, he could havefar right) that make three-dimensional objectsfrom poor balance when the nerves in theirtied a splint, but he knew there was no way to immediately stop the cascade of damagingbased on computer-generated drawings. This Cancer-Fighting Factory feet lose sensitivity. The insoles producechemical events happening those soldiers’ brains. So he went back to his lab to find onewide himself. view is a composite of seven photos.vibrations that override those effects.Bioengineer David Mooney has packed cancer-fighting factory into what looks like a tablet ofThe solution Parker hit upon is a “brain on a chip,” a model of the traumatized brain that is a The key to making them work was notaspirin. With this new technology, he aims to improve treatment of melanoma, a deadly skindecades first step since, toward his understanding work has proven the effects of TBIs and how to halt them. To replicate the braincancer that can claim up to 85 percent of patientssearchingdiagnosedforafteranmetastasis.ideal vibrationTo start,frequency,otherwise.in miniature,He hasParkerdemonstrated,and his team startedforwith an elastic substrate about the size of a fingernail,Mooney’s team members biopsied a mouse tumor, but isolated recognizing some of how its proteins, complex and systems loaded inthen added a layer of cells on top to mimic networks of blood vessels in the brain. To replicateexample, that exerting a mechanical force them into the tablet, a biodegradable plastic device nature—like so porous that weather, it is 90 for percent example—respondair. Theythe traumatic effects on vascular tissue fromon a cell can activate cell signaling.also filled the tablet with GMC-SF (granulocyte macrophage colony-stimulating factor), anan improvised explosive device, Parker andto random signals in the environment.inflammatory protein known to attract immune cells.At his the team first used committee a high-speed meeting motor to in stretch Cambridge,the elastic Massachusetts, substrate by Ingber one-fifth found of an himself inchBiomedical engineer James Collins, whoThen they implanted the tablet under the mouse’s skin. As expected, GMC-SF triggered ared alert, attracting immune cells that flooded theinventedtiny device.theOnceinsoles,inside,knewthesethatimmunethe actcellssurroundedin just a fewbymicroseconds,other scientiststhenbreakingreleasecame in contact with the tumor proteins and learned of walking to recognize is itself them a as complex well. Before system—a too long,it. When they analyzed the samples of theboundaries—physicists publishingcontents of the tablet, including the trained immune dynamic cells, were interplay trafficked of the to the ground, lymph the nodes, walker’ssubstrate about 90 minutes later, theyin biology journals, biologists in physicsbiological garrisons that help the body recognize and fight germs. Once ensconced inside,found no evidence of increased cell deathfootwear, the countless nerves that enervatethe trained immune cells taught naïve counterparts to recognize the tumor and attack. “We’republications. or even simple The tearing. group But resolved they did to find form athe feet, and the brain that governs theable to shuttle millions of cells through this device, generating a very potent immune responseresearch that the center stretched that cells not were only hypersensitivetolerated but against the cancer cells,” Mooney says.process. Suspecting that a person’s gait couldalsotoencourageda protein thatthepromotessame kindconstrictionof interdisciplinarysensibility, and whose ideas would be to a complete regression in 40 percent of mice the weather, Collins tried delivering randomofIn 2009, Mooney reported that the device led be just as responsive to random signals asblood vessels. To Parker, the results suggestthat head trauma kick-starts a chemicalinspired by the now-burgeoning knowledge with metastatic melanoma. Yet the projectchain of events leading to a narrowing andpulses to elderly subjects’ feet. Sure enough,might have stalled if not for the Wyss, whereabout reshaping how nature of blood builds. vessels in the brain.the signals worked. The sensitivity of theMooney has been working with collaboratorsto develop efficient and low-costSwiss-born Over time, Parker billionaire speculates, Hansjörg the effect Wyss,nerves in the subjects’ feet was so thoroughlya HarvardcontributesBusinessto longer-termSchoolconsequencesgraduate, liked manufacturing techniques and to prepare restored that they were able to walk with thesuch as depression and a wide variety ofthe idea so much that he donated the single the cancer-fighting factory for human balance of a typical 20-year-old.neurodegenerative diseases.largest gift in Harvard history, $125 million, trials. The first tests, in fewer than aParker hopes to eventually use theYet the shoe inserts almost didn’t happen.dozen patients, will take place at theto make “brain it on happen. a chip” to The test school drugs tapped that can Ingber haltCollins developed the basic technology overDana-Farber Cancer Institute this year.to run the process. the show. If a compound administereda decade ago and started a company toimmediately after the simulated explosionwere to stop the cascade of chemicalFilled with tumor-specific proteins and turn his prototype into an actual product.In Parker’s “brain on a chip” (top), brain cellsSole events, Searchingthen it could be used at the site ofimplanted under the skin, the porous plastic But by 2009, a foundering economy had leftcultured on silicone form neural networksIngber an injury, and I just stop as inside a soldier a gleaming, would tie a splintdisk David Mooney developed reprograms the(bottom). Rapidly stretching the cells at highthe project in the fledgling prototype stage.500-square-foot on a broken limb. laboratory space with airy,body’s immune system to attack tumors.speed mimics mechanical blast forces.That might have been the end of it—onehigh ceilings. Standing at a black counter-more idea in the boneyard of promisingTHIS PAGE, CLOCKWISE FROM TOP: JON CHASE/HARVARD; SAM OGDEN; MATTHEW HEMPHILL/HARVARD SCHOOL OF ENGINEERING AND APPLIED SCIENCES. OPPOSITE: WYSS INSTITUTE; PHOTO RESEARCHERS/SCIENCE SOURCEDISCOVER3504.2013