The first multi-organ chip made of human tissue can improve the treatment of diseases such as cancer

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The first multi-organ chip made of human tissue can improve the treatment of diseases such as cancer

The first multi-organ chip made of human tissue can be customized for patients to improve the treatment of diseases such as cancer.

In sci-fi movies, we often see science madmen doing experiments directly on the human body, so as to quickly obtain human data about certain drugs.

In reality, this seriously violates medical ethics and is obviously impossible to carry out.

But engineered tissues are a good alternative research model that can mimic the physiological or pathological state of the human body and help scientists quickly test the efficacy and safety of drugs.

It is worth noting that most of the existing engineered tissues are cultured independently, and the culture conditions of different engineered tissues are quite different.

Therefore, how to organically integrate a variety of engineered tissues to simulate body functions and systemic diseases, and how to allow these tissues to communicate physiologically as in the body, has become a difficult problem limiting the development of engineered tissues.

Recently, researchers from Columbia University in the United States published a cover paper entitled: A multi-organ chip with matured tissue niches linked by vascular flow in Nature Biomedical Engineering . The research developed a plug- and-play multi-organ chip the size of a microscope slide .

The chip consists of engineered tissues such as heart , bone , liver and skin that connect to circulating immune cells via vascular flow, enabling the reproduction of interdependent organ functions.

What’s more, this multi-organ chip can be tailored to the patient , which will ultimately enable personalized and optimized treatments for each patient as disease progression and response to treatment vary from person to person.

The first multi-organ chip made of human tissue can improve the treatment of diseases such as cancer

“This is a huge achievement for us, ” said Gordana Vunjak-Novakovic , a professor at Columbia University who led the project . ” We spent a decade conducting hundreds of experiments , exploring countless great ideas, and building many prototypes. , and now we have finally successfully developed the platform!

Inspired by the human body

In fact, integrating different engineered tissues such as heart, liver, bone, and skin tissues into one system is difficult because these tissues have distinct embryonic origins, structural and functional properties, and require unique and different nurturing environment.

Like many applications of bionics, the research team took inspiration from how the human body works.

They found that engineered tissue modules such as mature heart, liver, bone and skin could be connected by simulating circulatory vascular flow, allowing the interconnected organs to communicate as they do in the human body.

The first multi-organ chip made of human tissue can improve the treatment of diseases such as cancer Multi-Organ Chip Model

Dr. Kacey Ronaldson-Bouchard , lead author of the study , said: “Providing inter-organization communication while maintaining the individual phenotypes of different engineered tissues is an urgent challenge.

We chose to connect different engineered tissues through vascular circulation, a mimic of the way our organs connect in our bodies.

The optimized organization module can be maintained for more than a month

In the created multi-organ chip, each engineered tissue lives in its optimal culture environment and is separated from ordinary vascular flow by a selectively permeable endothelial barrier. Individual tissue environments are able to communicate through endothelial barriers and vascular circulation.

The researchers also introduced macrophage-producing monocytes into the vascular circulation, as they play an important role in directing tissue responses to injury, disease and treatment outcomes.

Tissue-specific niche multi-organ communication through vascular barrier and vascular flow

All engineered tissues were derived from the same line of human induced pluripotent stem cells (iPSCs) , obtained from small blood samples to demonstrate the system’s ability to conduct individualized, patient-specific studies.

To demonstrate that this model can be used for long-term studies, the research team preserved the already grown tissues for 4-6 weeks, and for an additional 4 weeks after vascular perfusion, these interconnected tissues maintained their molecular, structural and functional phenotypes.

Multi-organ tissue chip can maintain the phenotype of each organ after 4 weeks of culture

Using a multi-organ chip model to study anticancer drugs

The research team also wants to demonstrate how the model can be used to study important systemic diseases in humans, such as examining the side effects of anticancer drugs.

They investigated the effects of doxorubicin , a widely used cancer drug, on the heart, liver, bones, skin and blood vessels.

The results of the study show that the test data obtained by the multi-organ chip model are very close to the clinical research report .

Not only that, but the team developed a new multi-organ-on-a-chip computational model for mathematical simulation of drug absorption, distribution, metabolism, and secretion.

The model correctly predicted the metabolism and diffusion of doxorubicin within the chip.

This shows that the combination of multi-organ chips and computational methods in the future pharmacokinetic and pharmacodynamic studies of other drugs will provide a better foundation from preclinical to clinical, and will also help improve the drug development process.

Multi-organ tissue chip can predict the pharmacokinetics of doxorubicin treatment

The project leader, Professor Gordana Vunjak-Novakovic , said that it is worth noting that the multi-organ chip accurately predicted cardiotoxicity and cardiomyopathy, which usually requires clinicians to reduce the therapeutic dose of doxorubicin or even stop it. treat.

Overall, this study develops a plug-and-play, on-chip, multi-organ model that can help study the metabolism and response of anticancer drugs in humans, thereby accelerating drug discovery. In addition, the model can also be tailored to specific patients, thereby providing patients with optimal targeted treatment strategies.

It is reported that the research team is currently expanding the application of this multi-organ chip, including: breast cancer metastasis, prostate cancer metastasis, leukemia, the effect of radiation on human tissues, the effect of SARS-CoV-2 on the heart, lungs and blood vessels, ischemia Effects on the heart and brain, and drug safety and efficacy.

The team is also developing a user-friendly standardized chip for biology and clinical laboratories to help advance biological and medical research.

Professor Gordana Vunjak-Novakovic finally added:

I have been working on organ chips for 10 years, and I am still amazed by this research. We can simulate the physiology of patients by linking millimeter-sized tissues, including a beating heart, metabolic liver, Functional skin and bone grown from patient cells and more. We are excited about the potential of this approach, specifically designed to study systemic conditions associated with injury or disease, maintaining their interconnectedness while maintaining the biological properties of engineered human tissues . This will open entirely new doors for personalized therapy, tailoring treatments to individual patients.

Reference:

https://www.nature.com/articles/s41551-022-00882-6

https://www.engineering.columbia.edu/news/human-organ-chip-tissue-engineering

The first multi-organ chip made of human tissue can improve the treatment of diseases such as cancer

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