A New Plug-and-Play Multi-Organ Chip Has Been Concerned

A New Plug-and-Play Multi-Organ Chip Has Been Concerned ...

Engineered tissues have become a major component for estimating diseases and diagnosing the effectiveness and safety of drugs in a human way. Various engineered tissues can physiologically communicate, however, each individual tissue phenotypes must be maintained for weeks to months, as well as for biological and biomedical studies. Making the challenge even more complex is the necessity of combining tissue modules together to facilitate their physiological communication.

Multi-organ chip for plug-and-play, customized to the patient

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

We have spent ten years developing multibillion-dollar experiments, examining huge quantities of great ideas, and eventually developing this platform that successfully identifies organ interactions in the body, according to the project leader.Biomedical Engineering, Medical Sciences, and Dental Medicine, are among the areas that have shown a lot of interest in this project.

Inspired by the human body

The researchers used a human tissue-chip system to connect mature hearts, liver, bones, and skin tissue components, allowing interdependent organs to communicate just as they do in the human body. These tissues are distinct embryonic origins, structural and functional properties, and are adversely affected by cancer treatment drugs. This method is required to undergo rigorous testing.

While maintaining tissue fidelity, Kacey Ronaldson-Bouchard, the scientists'' lead author and an associate research scientist at Vunjak-NovakovicsLaboratory for Stem Cells and Tissue Engineering, believes the process of individual tissue development is fundamental. So we decided to carefully alter each tissue so that it behaves like the responses you would expect from the patient. So, we did not shy away from using patient-derived tissue models to maintain this advanced function when connecting multiple tissues. Unlikelyly,

Over a month, optimized tissue modules can be maintained.

By a selectively permeable endothelial barrier, the group created tissue modules that separated them from the common vascular flow. These monocytes were also introduced into the vascular circulation, owing to their important roles in directing tissue responses to injury, disease, and therapeutic outcomes.

Intensive, individual, patient-specific studies maintained all tissues, which had already been grown for four to six weeks, after being linked by vascular perfusion.

Using the model to study anticancer drugs

The researchers wanted to demonstrate how the model could be used for human treatment or to investigate the negative effects of anticancer drugs. They studied the effects of doxorubicin, a widely used anticancer drug, on heart, liver, bone, skin, and vasculature. They also found that the measured effects replicated those found in clinical trials of cancer therapy using the same drug.

The consortium developed in tandem a novel computational model of the multi-organ chip for drug molecular simulations of drugs absorption, distribution, metabolism, and secretion. This model correctly predicted doxorubicins metabolism into the chip, and its diffusion into the chip. This combination of the multi-organ chip and computational methodology in future studies of pharmacokinetics and clinical extrapolation provides a beneficial basis for preclinical to clinical extrapolation.

While doing this, we were able to identify some early molecular markers of cardiotoxicity, the main side-effect that limits the widespread use of the drug. According to Vunjak-Novakovic, the multi-organ chip predicted precisely the cardiotoxicity and cardiomyopathy that often require clinicians to decrease therapeutic dosages of doxorubicin or even stop the therapy.

Collaborations across the university

With Vunjak-Novakovic''s biomedical research, the lab''s collective expertise, Angela M. Christiano and her skin research team, Stanford University Professor, and professor professor, Rajesh K. Soni of the Proteomics Core at Columbia University.

A talion of approaches, allining individualized patient-specific contexts

The research team is experimenting with variations of this technology to provide the most customized patient-specific situations:breast cancer metastasis, prostate cancer metastasis, leukemia, and radiation treatment; 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 drugs. The group is also developing a user-friendly standardized chip for academic and clinical laboratories, which allows it to advance biological and medical studies

Vunjak-Novakovic added that after ten years of research on organs on chips, we still discover that this technique is effective in vivo therapy 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. We are excited about the potential of this technique. It will be specially designed for therapy of systemic illnesses related to injury or illness and will enable us to maintain the biological properties of modified human tissues one at a time

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