Stories about: organ-on-a-chip

Organs-on-chips reveal breathing’s critical role in lung cancer development

Image of lung cancer cells grown alongside human lung small airway cells inside an organ-on-a-chip
Inside view of a lung cancer chip: Lung adenocarcinoma cells are grown as a tumor cell colony (blue) next to normal human lung small airway cells (purple). Credit: Wyss Institute at Harvard University

One of the biggest challenges facing cancer researchers — and lots of other medical researchers, in fact — is that experimental models cannot perfectly replicate human diseases in the laboratory.

That’s why human Organs-on-Chips, small devices that mimic human organ environments in an affordable and lifelike manner, have quickly been taken up into use by scientists in academic and industry labs and are being tested by the U.S. Food and Drug Administration.

Now, the chips have helped discover an important link between breathing mechanics and lung cancer behavior.

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News notes: Headlines in science & innovation

An occasional roundup of news items Vector finds interesting.

Blood-brain barrier on chip

vector news - blood brain barrier chip
(Wyss Institute at Harvard University)

The blood-brain barrier protects the brain against potentially damaging molecules, but its gate-keeping can also prevent helpful drugs from getting into the central nervous system. Reporting in PLoS One, a team at the Wyss Institute for Biologically Inspired Engineering describes a 3-D blood-brain barrier on a chip — a hollow blood vessel lined with living human endothelial cells and surrounded by a collagen matrix bearing human pericytes and astrocytes.

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The design world’s eyes are on organs-on-chips

Organs-on-chips Museum of Modern Art MoMA London Design Museum exhibit Wyss Institute Vascular Biology
Organs-on-chips on display in New York City’s Museum of Modern Art. (Photo: Wyss Institute at Harvard University)

[Update 5/18/15: According to a Wyss Institute press release, the Design Museum in London has selected the organs-on-chips as the winner of their 2015 Designs of the Year exhibition’s Product category.]

If you’re in New York City in the next few months, pop into the Museum of Modern Art (MoMA) and stop by the “This Is For Everyone: Design For The Common Good” exhibit. There—alongside displays dedicated to the “@” symbol, the pin icon from Google Maps and bricks made from living mushroom roots—you’ll find three small silicone blocks mounted on a wall panel.

Those blocks are actually three of the organs-on-chips developed in the lab of Donald Ingber, MD, PhD, founding director of the Wyss Institute for Biologically Inspired Engineering and a scientist in Boston Children’s Hospital’s Vascular Biology Program.

Earlier this month, MoMA announced its plans to include the chips as part of their exploration of contemporary design in the digital age. In the museum’s eyes, organs-on-chips are more than a way to model disease in a complex, living system—they’re also art.

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A biospleen is born

biospleen sepsis Wyss Institute Donald Ingber
The Wyss Institute’s biospleen. (Photos courtesy Wyss Institute)

On a Friday morning a few years ago, a childhood friend of mine walked into his doctor’s office, saying his hip hurt. The pain was pretty severe, and had been getting worse for several days.

By Saturday morning, he was in intensive care, fighting for his life against an overwhelming case of sepsis. He survived, but at a cost: he’s now a quadruple amputee.

It’s people like him—and the other million-plus Americans who develop sepsis every year—that Donald Ingber, MD, PhD, and his team had in mind while developing the biospleen, a device that filters sepsis-causing pathogens from the blood. Announced to the world in September, the biospleen grew out of the organs-on-chips technology that Ingber’s team at the Wyss Institute for Biomedically Inspired Engineering launched commercially this past summer.

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The backstory behind organs-on-chips

Organs-on-chips drug testing drug discovery mechanobiology microfluidics Wyss Institute Vascular Biology Program
(Credit: Wyss Institute)

With the launch this summer of Emulate Inc., organs-on-chips—a disease-modeling platform we’ve covered several times on Vector—made the jump from academic to commercial development.

Though developed at the Wyss Institute for Biologically Inspired Engineering, the chips’ story actually began more than 20 years ago in Boston Children’s Hospital’s Vascular Biology Program (VBP). It’s a story that brings together characters from multiple fields and emerges from one fundamental concept: that mechanical forces are critical to the function and fate of cells, tissues and organs.

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‘Heart on a chip’ suggests a surprising treatment for a rare genetic disease

heart chip BarthIt was the variability that intrigued pediatric cardiologist William Pu, MD, about his patient with heart failure. The boy suffered from a rare genetic mitochondrial disorder called Barth syndrome. While he ultimately needed a heart transplant, his heart function seemed to vary day-to-day, consistent with reports in the medical literature.

“Often patients present in infancy with severe heart failure, then in childhood it gets much better, and in the teen years, much worse,” says Pu, of the Cardiology Research Center at Boston Children’s Hospital. “This reversibility suggests that this is a disease we should really be able to fix.”

Though it needs much more testing, a potential fix may now be in sight for Barth syndrome, which has no specific treatment and also causes skeletal muscle weakness and low white-blood-cell counts. It’s taken the work of multiple labs collaborating across institutional lines.

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Capturing complexity: Modeling bone marrow on a chip

Bone marrow on a chip organs on chips Wyss Institute Donald Ingber
Microscopic view of the engineered bone with an opening exposing the internal trabecular bony network, overlaid with colored images of blood cells and a supportive vascular network that fill the open spaces in the bone marrow-on-a-chip. (James Weaver, Harvard's Wyss Institute)

We’ve had a lung on a chip, and a gut on a chip. Now researchers at the Wyss Institute for Biologically Inspired Engineering have added another tissue to their list of “organs-on-chips”— devices that mimic in vitro tissues’ in vivo structure and function for pharmaceutical discovery and testing. In a paper published in Nature Methods, a team led by Donald Ingber, MD, PhD, (a member of Boston Children’s Hospital’s Vascular Biology Program and founding director of the Wyss), announced that they have developed “bone marrow-on-a-chip.”

The sheer complexity of the new device sets it apart from the Wyss’s previous organs, reflecting the greater natural complexity of bone marrow.

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Building a body, one organ chip at a time

It may not look like it, but it's a lung, just in chip form.

They don’t look like much sitting in your hand. A few pieces of clear plastic, each smaller than an Altoids tin, with channels visible inside and holes for plugging tubing into them.

But fill them with cells and treat those cells the right way, and they turn into something amazing: tiny hearts, lungs, guts, kidneys.

They’re “organs on chips,” and they represent what’s probably the most comprehensive effort to date to physically model the functions of whole organs for drug development and disease research.

Developed by a team of biologists and engineers led by Donald Ingber, MD, PhD, a member of Boston Children’s Hospital’s Vascular Biology Program and director of the Wyss Institute for Biologically Inspired Engineering at Harvard, they’re the building blocks for an ambitious project to create an artificial multi-organ system—essentially, a whole body on a chip.

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Drug-testing alternative: a lung on a chip


Combining microfabrication techniques from the computer industry with modern tissue engineering, a team at Children’s Hospital Boston and Harvard’s Wyss Institute for Biologically Inspired Engineering has created a device that mimics the function of a human lung. This living “lung-on-a-chip,” which incorporates human lung and blood-vessel cells, reproduces the all-important interface between the lung’s tiny air sacs and the bloodstream. Breathing is simulated with a vacuum pump.

The wafer-sized device mimics the human lung’s response to infectious agents, airborne particles and toxins in a way that’s truer to real life than standard cell testing in a lab dish.

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