Why scientists engineered a chip that has a tiny heart and liver

By Mark Waghorn via SWNS

A multi-organ chip containing a tiny heart and liver engineered from human tissue has been created by scientists at Columbia University.

It also contains real bone and skin. They are linked by vascular flow with circulating immune cells.

The device is about the size of a glass microscope slide - and can be used to test the efficacy of drugs.

Up to four organs measuring just a millimetre in size can be cultured.

They are grown from a patient's own cells - offering customisation for improved modelling of cancer and other systemic diseases.

Project leader Professor Gordana Vunjak-Novakovic, of Columbia University, New York, said: "This is a huge achievement for us.

"We've spent ten years running hundreds of experiments, exploring innumerable great ideas and building many prototypes.

"Now at last we've developed this platform that successfully captures the biology of organ interactions in the body."

The system enables inter-dependent organs to communicate - just as they do in the real thing.

Particular tissues were selected because they have distinctly different embryonic origins and structural and functional properties.

They are adversely affected by cancer drugs - presenting a rigorous test of the proposed approach.

Lead author Dr. Kacey Ronaldson-Bouchard, from the same lab, said: "Providing communication between tissues while preserving their individual phenotypes has been a major challenge.

"We focus on using patient-derived tissue models. We must individually mature each tissue so it functions in a way that mimics responses you would see in the patient.

"We don't want to sacrifice this advanced functionality when connecting multiple tissues.

"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 our organs are connected within the body."

Tissue modules were developed - each within its optimized environment and separated by a permeable endothelial barrier.

They were able to communicate by vascular circulation. The researchers also introduced monocytes and macrophages.

These are immune cells that direct tissue responses to injury, disease and therapeutic outcomes.

All tissues were derived from the same line of human-induced pluripotent stem cells (iPSC) obtained from a small sample of blood.

This demonstrated the potential for personalised medicine and long-term studies. Tissues were grown and matured for four to six weeks.

They were then maintained for an additional four weeks - after they were linked by vascular perfusion.

The researchers also investigated the effects of doxorubicin - a broadly used cancer drug - on the heart, liver, bone, skin and vasculature.

They showed the measured effects recapitulated those reported from clinical studies of the same drug.

A computational model of the chip correctly predicted its metabolism and diffusion - opening the door to improvements in drug development.

Prof Vunjak-Novakovic said: "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."

The chip's structure began with the heart, liver and vasculature - nicknamed the HeLiVa platform.

Variations are now being used to study patient-specific breast and prostate cancer spread and leukaemia.

The researchers are also looking at the effects of COVID-19 on heart, lung and blood vessels and the safety and effectiveness of drugs.

The group is also developing a user-friendly standardised chip for both academic and clinical laboratories, to help utilise its full potential for advancing biological and medical studies.

Added Prof Vunjak-Novakovic: "After ten years of research on organs-on-chips, we still find it amazing we can model a patient's physiology by connecting millimeter-sized tissues - the beating heart muscle, the metabolising liver, and the functioning skin and bone that are grown from the patient's cells.

"We are excited about the potential of this approach. 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 chip is described in the journal Nature Biomedical Engineering.