A new plug-and-play multi-organ chip has been developed

A new plug-and-play multi-organ chip has been developed ...

Engineered tissues have become a major component for assessing diseases and developing the effectiveness and safety of drugs in a human environment. Nevertheless, it is vital to keep each engineered tissue with its own environment, ensuring that the specific tissue phenotypes can be maintained for weeks to months, as required for biological and biomedical studies. Make the challenge even more complicated is the necessity of connecting tissue modules together to facilitate their physiological communication, without sacrificing the individual engineered tissue environments.

A novel plug-and-play multi-organ chip, specifically designed for patients, is being developed.

Up until now, no one has been able to meet both conditions. Today, a team of researchers fromColumbia EngineeringandColumbia University Irving Medical Center claims they have developed a human physiology model in the form of a microscope slide, which can be customized to the patient. Because disease progression and treatment reactions vary greatly from one person to another, such a chip will eventually enable personalized treatment for each individual. Thestudyis the cover story of the April 2022 issue ofNature Biomedical Engineering

Weve developed this platform, which allows for ten years to study hundreds of experiments and testing, and now at least we have successfully captured the biology of organ interactions in the body, according to the project leader.

Inspired by the human body

Using their expertise from how the human body works, the team has built a human tissue-chip system in which they interconnected mature heart, liver, bone, and skin tissue components, allowing for interdependent organs to communicate as they do in the human body. These tissues are selected because they have radically different embryonic origins, structural and functional properties, and are adversely affected by cancer treatment treatments. The results have been conducted in a rigorous testing of the proposed approach.

The study''s lead author and an associate research scientist, Kacey Ronaldson-Bouchard, has found that when applied to patient-derived tissue models, each tissue must be adapted accordingly to meet the patient''s needs, while simultaneously maintaining its biological fidelity. So, we decided to keep the tissue unchanged by storing circulating cells and thus increasing the number of different organs that are connected within the body.

The use of optimized tissue modules can last for more than a month.

Combined with a selectively permeable endothelial barrier, the group created tissue modules that separated them from the common vascular flow. These monocytes have also been introduced into the vascular circulation, owing to their significant roles in regulating 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, in order to demonstrate the feasibility for personalized patient-specific studies. And, to prove that the model may be utilized for long-term studies, the team maintained the tissues, which had already been grown and matured for four to six weeks, for an additional four weeks.

Using the model to study anticancer drugs

Researchers sought to demonstrate how the model might be used for human evaluations of an important systemic condition and decided to investigate the detrimental effects of anticancer drugs. They investigated the effects of doxorubicin, a broadly used anticancer medication, on heart, liver, bone, skin, and vasculature. These tests uncovered that the measured effects resumed those obtained from clinical studies of cancer therapy using the same medication.

The group developed a novel computational model of the multi-organ chip for drug testing of drugs absorption, distribution, metabolism, and secretion. This model correctly predicted doxorubicins metabolism into doxorubicinol and its diffusion into the chip. The combination of the multi-organ chip and computational methodology in future research of pharmacokinetics and clinical extrapolation provides an improved basis for preclinical to clinical extrapolation.

Despite this, we were able to identify early molecular markers of cardiotoxicity, the main side-effect that limits the wide use of the medication. In contrast, the multi-organ chip predicted precisely the cardiotoxicity and cardiomyopathy that often require clinicians to lower therapeutic dosages of doxorubicin or even to stop the therapy," said Vunjak-Novakovic.

Collaborations across the university

The development of the multi-organ chip began from a platform with the heart, liver, and vasculature, nicknamed theHeLiVaplatform. As always with Vunjak-Novakovics biomedical research, collaborations were necessary, according to Angela M. Christiano and her skin research team (Columbia University), Rajesh K. Soni of the Proteomics Core at Columbia University, and the computational modeling support of the CFD Research Corporation.

A diverse set of applications, allin one-off patient-specific contexts.

The research team is currently experimenting with variations of this technology to evaluate in individualized patient situations:breast cancer metastasis; prostate cancer leukemia; the effect of radiation on human tissues; the effects of SARS-CoV-2 on the heart, lung, and vasculature; the effects of ischemia on the brain and the safety and effectiveness of medications.

After ten years of research on organs on chips, we still find it amazing that we can model a patient physiology by connecting millimeter sized tissues the beating heart muscle, the metabolizing liver, and the functioning skin and bone that are grown from the patients cells. This technique is uniquely designed for individuals who are injured 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!

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