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Organs-on-Chips Present Innovative Model for Drug Development

Researchers like Dan Huh, a University of Pennsylvania assistant professor of bioengineering, are growing human cells on plastic chips and using them to study the effects of drugs on hard-to-treat diseases. | John Carlano

Blinking eye cells on a polymer chip – along with other “organs-on-chips” – offer a new way to examine the effects of drug treatments on humans, according to the panelists of a Feb. 16 news briefing at the 2018 AAAS Annual Meeting.

Working at the intersection of biology and engineering, researchers grow cells specific to a vital organ – such as a liver or a lung – and reproduce the environment of the organ on a small, flexible polymer chip, creating “a home away from home” for the cells, said Geraldine Hamilton, president and chief scientific officer of Emulate Inc., which develop organs-on-chips technology. The organs-on-chips can then be used to test the efficacy of drug treatments on a particular organ.

“Some of the technologies that we’re talking about could really revolutionize our ability to expedite the way which we evaluate new treatments, allowing us to understand far more thoroughly than we have in the past whether or not there is potential for them to be harmful,” said Robert Urban, the global head of Johnson & Johnson Innovation.

Hamilton, left, Urban and Huh discussed their work using “organs-on-chips” to advance drug development and the promise of the devices as tools for studying disease treatment effects. | Professional Images Photography

Organs-on-chips offer benefits over existing methods for drug discovery and development, panelists said. “They are more true-to-life than cells in dishes and more human-like than animal models,” said Hamilton. Additionally, using organs-on-chips for testing avoids unnecessarily exposing patients to drug treatments that might be ineffective or have harmful side effects, Urban added.

The human blinking eye-on-a-chip, developed by Dan Huh, assistant professor of bioengineering at the University of Pennsylvania, is designed to mimic the surface of the human eye. The blinking eye is created by culturing cells of the cornea and the translucent membrane of the inner eyelid on a 3D-printed scaffold shaped like a contact lens. By adding a hydrogel that mimics blinking, Huh can model complex ocular diseases such as dry eye. Despite the disease being extremely common, as of last year, there was only one FDA-approved treatment for dry eye, Huh said.

Several different organs-on-chips have been created, the panelists said, including a placenta chip and brain chip. Hamilton announced the newest organ-on-chip innovation, which recreates an intestinal lining using patient-derived stem cells, created through a partnership between Emulate and Cedars-Sinai Board of Governors Regenerative Medicine Institute. Just as they do in the human body, the cells form intestinal folds on the chip.

Studying the effects of drug treatment on the intestinal lining presents a challenge, Hamilton said, because of the presence of the microbiome and the complexity of the layer of cells in the intestinal linings, known as the epithelium. Such complexities are not accounted for in animal models, Hamilton said. The intestinal lining chip can be used for the testing of treatments for inflammatory gastrointestinal diseases with a genetic component, such as Crohn’s disease, ulcerative colitis and irritable bowel syndrome.

The inclusion of a patient’s “genetic fingerprint” demonstrates another benefit of organs-on-chips: a source for precision medicine and personalized health by testing how an individual would respond to a treatment, Hamilton said.

Huh has developed an “eye-on-a-chip,” by creating a 3-D printed, life-sized eyeball that can realistically replicate complex ocular diseases like dry eye syndrome. | University of Pennsylvania

Despite the complexity of the biology, the simplicity of the chip’s engineering allows it to serve as a footprint for diverse types of organs-on-chips, Hamilton said. This flexibility allows the organs-on-chips to be used in many different laboratories and spurs “democratization” of the technology, she said.

The intersection of biology and engineering was a theme AAAS President Susan Hockfield cited in her President’s Address on Feb. 15. Hockfield, a neuroscientist at the Massachusetts Institute of Technology and former president of the university, said the story of the 21st century might well be the convergence of biology and engineering.

Answering engineering questions with biological advances – and vice versa – offers solutions to “the most daunting problems that face us,” Hockfield said.

The panel, which brought together experts from academia and industry, also echoes the theme of the 2018 Annual Meeting, “Advancing Science: Discovery to Application.” Recognizing the role of industry in the scientific enterprise, calls upon scientists to “work together with renewed energy across the full spectrum of the scientific enterprise—and across the sectors that advance it.”

[Associated image: Emulate Inc.]