US researchers model multiple organs on a microslide-sized chip

Newly developed chips will help us to fight diseases like cancer
Ameya Paleja
The multi-organ chip at workColumbia Engineering

Researchers at the Columbia University's Engineering School in collaboration with colleagues at Irving Medical Center, have developed an organ-on-a-chip system consisting of tissues of the human heart, liver, bone, and skin as well as circulating immune cells to mimic the physiology of the human body, said a university press release.

Engineering tissues are now the mainstay of disease models, providing the ideal conditions for disease progression and drug efficacy. However, the human body is a collective of tissue types that do not work in isolation but communicate physiologically. So, researchers are working on developing organ-on-a-chip systems that can mimic the human body, providing more information on how diseases progress and the effect of drugs on other organs. 

Mimicking the human body and unique to individuals

The multi-organ-on-a-chip system developed by the researchers is only the size of a microscope slide. It consists of the human heart, bone, liver, and skin tissues, each unique in its embryonic origin, structural and functional properties, and requiring its own independent environment. The organ tissues are all linked by the vascular flow of immune cells. The researchers achieved this unique distinction by using endothelial barriers that are selectively permeable. 

Interestingly, the tissue types present on the chip system are developed from the same cell line as the human-induced pluripotent stem cells (iPSC) technology lets researchers create patient-specific lines from a small sample of blood drawn from an individual. 

While the growing and maturation of the tissue type took four-to-six weeks, the researchers were also able to maintain these tissues in their individual environments for another four weeks.

Studying anticancer drugs

During this period, the researchers studied the effects of the anti-cancer drug doxorubicin, which is broadly used among patients and well reported to have adverse effects. The team developed a novel computational model to simulate the drug's absorption, distribution, metabolism, and secretion on the multi-organ chip and verified its accuracy by studying the doxorubicin's metabolism.

"We were able to identify some early molecular markers of cardiotoxicity, the main side-effect of the drug. The multi-organ chip precisely predicted the cardiotoxicity and cardiomyopathy that often require clinicians to decrease therapeutic dosages of doxorubicin or even to stop the therapy," said project leader Gordana Vunjak-Novakovic. 

The computational models can be used in future studies to accurately predict the pharmacodynamic outcomes of other drugs and help in extrapolating effects on clinical outcomes. 

The team is currently using variations of the chip to study metastasis in breast cancer, prostate cancer, leukemia, effects of ischemia on other organs, as well the impact of SARS-CoV-2 infection on the heart, lung, and vascular system, the press release said.

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