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Gut Tissue From Stem Cells Simulated on Organ Chips

Clive Svendsen

Clive Svendsen speaking at the AAAS annual meeting, 17 February 2018 (A. Kotok)

17 February 2018. Researchers created working human gut tissue cells derived from stem cells, grown on plastic chips simulating intestinal diseases, as a tool for testing effectiveness and safety of treatments before given to patients. Speakers from Cedars-Sinai Medical Center and the company Emulate Inc. described their findings today at the annual meeting of American Association for Advancement of Science, or AAAS, in Austin, Texas.

In addition, Cedars-Sinai, in Los Angeles, plans to advance the organ-on-a-chip technology into its precision medicine program, to be called Patient-on-a-Chip, for identifying treatments reflecting an individual’s condition and molecular make-up. Science and Enterprise learned Cedars-Sinai and Emulate Inc., in Boston, expect to announce the program next week.

Organs-on-chips, as the name implies, are small flexible polymer plastic devices with fine channels etched in the surface or drilled through, lined with live tissue and cells, and designed to simulate the workings of human organs. As explained by Geraldine Hamilton, president of Emulate Inc. at the AAAS meeting, the 3-D tissues on the devices make it possible to predict the behavior of human organs better than animal models like mice, and cells growing in lab cultures. Organs-on-chips, said Hamilton, simulate the flow, dynamics, and environment of complex systems in organs, enabling the “control of biology, but also the physics that controls the biology.”

Clive Svendsen, one of the leaders of the Cedars-Sinai initiative, outlined the role of human induced pluripotent stem cells — also known as adult stem cells, derived from existing tissue rather than embryos — in creating organ-on-chip devices for precision medicine. Svendsen, with colleagues at Cedars-Sinai and Emulate Inc., created an intestine chip with stem cells to reflect the unique genomics of the person supplying the stem cells, first producing organoids, then growing 3-D intestinal tissue.

The team used the intestine chips to simulate inflammatory bowel disease, a gastrointestinal disorder. A paper published in December 2017 describes the process, where an enzyme associated with the disorder produce characteristic reactions of inflammatory bowel disease in the epithelial cells lining the intestine chip. In addition, the reactions of these cells in the intestine chips better simulate the disease than comparable cells in organoids alone.

Lung-on-chip

Lung-on-chip device (Emulate Inc.)

Brain, lung, liver, eyes, blood clots

“We can produce an unlimited number of copies of this tissue and use them to evaluate potential therapies,” says Svendsen in a joint Cedars-Sinai and Emulate Inc. statement. “This is an important advance in personalized medicine.” Cedars-Sinai plans to apply intestine chips as part of its precision medicine program, beginning with early-onset inflammatory bowel disease, a form of the disorder affecting young children. Svendsen’s lab is also developing a chip simulating the blood-brain barrier for research on neurodegenerative disorders including amyotrophic lateral sclerosis, or ALS, and Parkinson’s disease.

Hamilton says Emulate Inc., a spin-off enterprise from the Wyss Institute at Harvard University, is developing airway and lung chips to test for respiratory disorders, and liver chips that can help find toxicities in drugs more reliably than lab animals. As reported by Science & Enterprise, Emulate and the Food and Drug Administration are also assessing the ability of organs-on-chips to fulfill regulatory needs for testing drugs, as well as food, dietary supplements, and cosmetics.

Dan Huh, a bioengineering professor at University of Pennsylvania in Philadelphia and the AAAS panel’s moderator, described his lab’s work developing a human eye on a chip that not only the mimics the eye’s physiology, but simulates its blinking actions as well. Huh’s group is also working with NASA on testing immune system cells in microgravity, a critical concern for extended space travel.

Robert Urban, head of Johnson & Johnson Innovation in Cambridge, Massachusetts, described for the AAAS audience development of a chip device that helped resolve problems with a synthetic antibody for treating systemic lupus erythematosus, commonly known as lupus, an autoimmune disorder. Working with Emulate Inc., an organ chip was able to identify the mechanism forming blood clots caused by the antibody, which were not revealed in preclinical tests with animals.

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Disclosure: The author owns shares in Johnson & Johnson.

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