Patient-on-a-Chip progresses

Organ-on-a-chip tech recreates human intestinal lining; program launched to test chips in treatment selection

Kelsey Kaustinen
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LOS ANGELES & BOSTON—Cedars-Sinai and Emulate Inc. are furthering their long-term business relationship with the announcement of a Patient-on-a-Chip program that will seek to use lab-on-a-chip technology and patient-derived cells to determine ideal treatment approaches for individuals.
 
Emulate launched in 2014, with Cedars-Sinai as one of its investors, and early findings from initial stem cell work on Organ-Chips were shared in October 2015, according to Dr. Geraldine A. Hamilton, president and chief scientific officer of Emulate. The Patient-on-a-Chip program is a collaborative effort between Emulate and the Cedars-Sinai Regenerative Medicine Institute, with patients participating through research programs at Cedars-Sinai. Hamilton says specific details about future studies and diseases of focus are not yet being disclosed.
 
“The medical potential of a Patient-on-a-Chip is extraordinary,” said Dr. Clive Svendsen, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. “As examples, scientists could use Organs-on-Chips to create a living model of a patient with Parkinson’s disease, amyotrophic lateral sclerosis or Crohn’s disease, a debilitating inflammatory bowel disorder linked to several gene mutations. By flowing drugs through Organ-Chips containing the patient’s own cells and tissue, we could predict which treatment is most beneficial for that patient.”
 
Some of the organizations’ most recent work with this technology, announced in February, consists of successfully recreating human intestinal lining on Intestine-Chips. These chips enable scientists to create a duplicate of a patient’s gastrointestinal lining and test a variety of drugs to determine an ideal treatment plan. Investigators at the Cedars-Sinai Board of Governors Regenerative Medicine Institute and Emulate ran the study, with the findings published in Cellular and Molecular Gastroenterology and Hepatology in an article titled “Enhanced Utilization of Induced Pluripotent Stem Cell–Derived Human Intestinal Organoids Using Microengineered Chips”
 
Induced pluripotent stem cells were provided by Cedars-Sinai, reprogrammed from skin and blood cells into induced pluripotent stem (iPS) cells and then differentiated into intestinal cells. Organoids were grown from the iPSCs, and sample cells were inserted into Emulate’s Intestine-Chip.
 
The company’s Organ-Chips are engineered out of a flexible polymer with tiny channels that can be lined with a variety of live cells. Roughly the size of AA batteries, these chips recreate the microenvironment of the intestine, including the intestinal epithelium. When fluids are passed through the channels, it mimics the natural internal environment and allows the cells to develop 3D villi-like structures as in a normal intestine. With the combination of these technologies, all key cell types can be replicated ex vivo.
 
“Emulate’s Human Emulation System—a lab-ready system which includes Organ-Chips, instrumentation and software apps—recreates true-to-life biology outside the body, so that the cells can be in a ‘home away from home,’” Hamilton tells DDNews. “The technology recreates the natural physiology and mechanical forces that cells experience within the human body, so that the induced pluripotent stem cells can grow and thrive as they would inside the human body. In general, the Human Emulation System has the advantage of being designed as a lab-ready system that can be used by any researcher. This technology creates an environment where the cells exhibit an unprecedented level of biological function, and provides control of complex human biology and disease mechanisms not possible with existing techniques.”
 
In addition to the Intestine-Chip, Hamilton says Emulate also has Organ-Chips for the lungs, liver and kidney, and is in the process of developing skin, heart and blood-brain barrier versions as well.
 
“By creating a personalized Patient-on-a-Chip, we can really begin to understand how diseases, medicines, chemicals and foods affect an individual’s health,” she added. “The goal of Emulate working with Cedars-Sinai is to advance and qualify the system for new clinical applications and ultimately democratize the technology so that it can have broad impact on patient healthcare.”
 
“Cedars-Sinai’s world-class stem cell expertise and discovery, combined with Emulate’s pioneering Human Emulation System, is poised to reshape the future of medical care,” remarked Shlomo Melmed, executive vice president of academic affairs and dean of the medical faculty at Cedars-Sinai. “This project is an important initiative of Cedars-Sinai Precision Health, whose goal is to drive the development of the newest technology and best research, coupled with the finest clinical practice, to rapidly enable a new era of personalized health.”
 
Just a handful of days after sharing the news about the progress with Intestine-Chips, Emulate announced that it would be partnering with two leading pharmaceutical companies. Emulate will be teaming up with F Hoffman La-Roche AG to apply its Human Emulation System across R&D programs for human-relevant studies to better predict the safety and efficacy of drug candidates, with a focus on discovering and developing new therapeutic antibodies and drug combinations. The second partnership, this one with Takeda Pharmaceutical Co. Ltd., will focus specifically on the Intestine-Chip. The companies will leverage the technology in a variety of Takeda’s R&D work to “expand innovation in the drug discovery process for gastrointestinal diseases.” Their focus will be on programs in which the Intestine-Chip can answer questions about intestinal epithelium function and its role in gastrointestinal diseases such as inflammatory bowel disease.

Kelsey Kaustinen

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