Organs on a chip

The new multi-organ chip has the size of a glass microscope slide and allows the culture of up to four human engineered tissues, whose location and number can be tailored to the question being asked. These tissues are connected by vascular flow, but the presence of a selectively permeable endothelial barrier maintains their tissue-specific niche.

NEW YORK — A new plug-and-play chip containing samples of your heart, liver, and other organs could soon help doctors customize treatments for patients battling diseases like cancer.

A team from Columbia University have created this organ-on-a-chip using engineered human heart, bone, liver, and skin tissue, linked by vascular flow with circulating immune cells. The device is about the size of a glass microscope slide and study authors say they can use it to test the efficacy of drugs.

Importantly, this could provide personalized test results for patients, since responses to medical treatments often vary from person to person. The chip can culture up to four organs at once. Scientists grow them from a patient’s own cells, offering improved modeling of cancer and other systemic diseases.

“This is a huge achievement for us—we’ve spent ten years running hundreds of experiments, exploring innumerable great ideas, and building many prototypes, and now at last we’ve developed this platform that successfully captures the biology of organ interactions in the body,” says project leader Professor Gordana Vunjak-Novakovic in a university release.

Replicating the connected nature of your organs

The system also allows interdependent organs to communicate, just as they do in the human body. Researchers selected particular tissues because they have distinctly different embryonic origins and structural and functional properties. Cancer drugs also adversely affect these particular organs, presenting a rigorous test of the proposed approach.

“Providing communication between tissues while preserving their individual phenotypes has been a major challenge,” adds lead author Dr. Kacey Ronaldson-Bouchard.

“Because we focus on using patient-derived tissue models we must individually mature each tissue so that it functions in a way that mimics responses you would see in the patient, and we don’t want to sacrifice this advanced functionality when connecting multiple tissues,” Ronaldson-Bouchard continues.

“In the body, each organ maintains its own environment, while interacting with other organs by vascular flow carrying circulating cells and bioactive factors. So we chose to connect the tissues by vascular circulation, while preserving each individual tissue niche that is necessary to maintain its biological fidelity, mimicking the way that our organs are connected within the body.”

The team developed tissue modules containing an optimized environment for each sample, separated by a permeable endothelial barrier. The tissue samples were able to communicate by vascular circulation. The researchers could also introduce monocytes and macrophages to the chip. These are immune cells that direct tissue responses to injury, disease, and therapeutic outcomes.

Cancer drugs affect the chip just like they do a real person

Scientists derived all of the tissues from the same line of human-induced pluripotent stem cells (iPSC) obtained from a small sample of blood. This demonstrated the potential for personalized medicine and long-term studies. The tissues then grew and matured for four to six weeks. Researchers then maintained the cells for an additional four weeks before linking them through vascular perfusion.

The researchers also investigated the effects of the common cancer drug doxorubicin on the chip’s heart, liver, bone, skin, and vasculature samples. Results show the drug’s effect on the organs mimicked those reported during clinical studies using the same drug. A computational model of the chip correctly predicted its metabolism and diffusion, opening the door to improvements in drug development.

“While doing that, we were also able to identify some early molecular markers of cardiotoxicity, the main side-effect that limits the broad use of the drug. Most notably, the multi-organ chip predicted precisely the cardiotoxicity and cardiomyopathy that often require clinicians to decrease therapeutic dosages of doxorubicin or even to stop the therapy,” Prof. Vunjak-Novakovic says.

organ chip
In their study, researchers cultured liver, heart, bone, and skin, connected by vascular flow for four weeks. These tissues can be generated from a single human induced pluripotent stem cell, generating a patient-specific chip, a great model for individualized studies of human disease and drug testing. (Photo credit: Keith Yeager/Columbia Engineering)

Could the organ-on-a-chip help COVID research?

The chip’s structure — nicknamed the HeLiVa platform — began with the heart, liver, and vasculature. Variations are now in use to study the spread of patient-specific breast and prostate cancers and leukemia cases.

The researchers are also looking at the effects of COVID-19 on heart, lung, and blood vessels, and the safety and effectiveness of new COVID treatments. The group is also developing a user-friendly standardized chip for both academic and clinical laboratories, to help utilize its full potential for advancing biological and medical studies.

“After ten years of research on organs-on-chips, we still find it amazing that we can model a patient’s physiology by connecting millimeter-sized tissues—the beating heart muscle, the metabolizing liver, and the functioning skin and bone that are grown from the patient’s cells. We are excited about the potential of this approach,” Vunjak-Novakovic concludes.

“It’s uniquely designed for studies of systemic conditions associated with injury or disease, and will enable us to maintain the biological properties of engineered human tissues along with their communication. One patient at a time, from inflammation to cancer!”

The new chip is described in the journal Nature Biomedical Engineering.

South West News Service writer Mark Waghorn contributed to this report.

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