Medical treatment

Ready-to-use multi-organ chip can personalize the medical treatment of diseases

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

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

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

“This is a huge achievement for us – we’ve spent ten years conducting hundreds of experiments, exploring countless great ideas and building lots of prototypes, and now we’ve finally developed this platform that captures with success in the biology of organ interactions in the body,” says Professor Gordana Vunjak-Novakovic, project leader, in a statement from the university.

Reproduce the connected nature of your organs

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

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

“Because we are focused on using patient-derived tissue models, we have to individually mature each tissue to function in a way that mimics the responses you would see in the patient, and we don’t want to sacrificing this advanced functionality when connecting multiple fabrics,” continues Ronaldson-Bouchard.

“In the body, each organ maintains its own environment, while interacting with other organs through vascular flows carrying circulating cells and bioactive factors. We have therefore chosen to connect the tissues by vascular circulation, while preserving each individual tissue niche necessary to maintain its biological fidelity, mimicking the way our organs are connected within the body.

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

Cancer drugs affect the chip like they do a real person

The scientists derived all the tissues from the same line of human induced pluripotent stem cells (iPSCs) obtained from a small blood sample. This demonstrated the potential for personalized medicine and long-term studies. The tissues then grew and matured for four to six weeks. The researchers then maintained the cells for another four weeks before connecting them by vascular perfusion.

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

“By doing so, we were also able to identify some early molecular markers of cardiotoxicity, the main side effect that limits the large-scale use of the drug. Most notably, the multi-organ chip accurately predicted cardiotoxicity and cardiomyopathy that often compel clinicians to reduce therapeutic doses of doxorubicin or even discontinue therapy,” explains Prof. Vunjak-Novakovic.

In their study, the 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 microarray, an excellent 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 structure of the chip – dubbed the HeLiVa platform – started with the heart, liver and vasculature. Variants are now being used to study the spread of patient-specific breast and prostate cancers and leukemia cases.

Researchers are also studying the effects of COVID-19 on the heart, lungs and blood vessels, as well as the safety and effectiveness of new COVID treatments. The group is also developing a standardized chip that is user-friendly for academic and clinical laboratories, to help use its full potential to advance biological and medical studies.

“After ten years of organ-on-chip research, we still find it amazing to be able to model a patient’s physiology by connecting millimeter tissues – the beating heart muscle, the metabolizing liver, and the functional skin and bones that are developed from the patient’s cells. We are excited about the potential of this approach,” concludes Vunjak-Novakovic.

“It is specifically designed for studies of systemic conditions associated with injury or disease, and will allow us to maintain the biological properties of altered human tissues as well as their communication. One patient at a time, from inflammation to cancer!

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

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