Engineered tissues have become a critical component for determining diseases and developing the effectiveness and safety of drugs in a human context. Several engineered tissues have, however, been used to develop physiological interactions that are consistent with the individual human tissues. Rather, each individual individual organ structure requires a mix of tissue elements to provide additional physiological communication.
A novel plug-and-play multi-organ chip that is customized to the patient
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 allows the patient to recapitulate interdependent organ functions. Because disease progression and responses to treatment vary greatly from one person to another, such a chip will eventually assist personalized therapy for each patient. Thestudy is the cover story of the April 2022 issue ofNature Biomedical Engineering.
This is a significant achievement for usweve spent ten years designing and experimenting with unnumerable fantastic ideas, and now we have developed this platform that effectively identifies the biology of organ interactions in the body, according to the project leader.
Inspired by the human body
The researchers formulated a human tissue-chip system in which they linked mature heart, liver, bone, and skin tissue structures, allowing interdependent organs to communicate as they do in the human body. These tissues have distinctly different embryonic origins, structural and functional properties, and are adversely affected by cancer treatment medications.
While maintaining tissue integrity, Kacey Ronaldson-Bouchard, the research head and an associate researcher at Vunjak-NovakovicsLaboratory for Stem Cells and Tissue Engineering, believes this is because we focus on using patient-derived tissue models. Because we prefer to use patient-derived tissue approaches, we must individually mature each tissue so that it functions in an individual way, mimicking responses seen in the patient. So, we chose to maintain each individual tissue niche that is required to maintain its biological
The utilization of optimizing tissue modules can last for more than a month.
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, causing tumors to flourish. This helps the researchers in identifying tissue responses to injury, illness, and therapeutic goals.
All tissues were collected from a small sample of blood using iPSC, in order to demonstrate the capability for individual patient-specific research. And, to prove the model can be used for long-term experiments, the team maintained the tissues, which had already been grown and matured for four to six weeks, for another four weeks.
Using the model to study anticancer drugs
Researchers also wanted to demonstrate how the model might be used for human treatment and chosen to investigate the harmful effects of anticancer drugs. They investigated the effects of doxorubicin, a broadly used anticancer medication, on the heart, liver, bone, skin, and vasculature. They also determined that the measured effects were recapitulated from clinical studies of cancer therapy using the same medication.
The multi-organ processor has developed a novel computational model for 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 processor and computational methods in future experiments of pharmacokinetics and clinical extrapolation offers a better understanding of the drug development pipeline.
While doing that, we were also able to identify some early molecular markers of cardiotoxicity, the principal 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
The development of the multi-organ chip took place from a platform with the heart, liver, and vasculature, now known as theHeLiVaplatform. As always, collaborations were critical for completion of Vunjak-Novakovics biomedical research, including Angela M. Christiano, and her skin research team (Columbia University), Rajesh K. Soni of the Proteomics Core at Columbia University, and the combined computational modeling support of the CFD Research
A slew of possibilities, all in patient-specific scenarios, are integrated.
The research team is currently developing a user-friendly standardized processor for both academic and clinical laboratories to assist in its development.
After ten years of research on organs-on-chips, we still find it amazing that we can develop patients physiology by connecting millimeter sized tissues the beating heart muscle, the metabolizing liver, and the functioning skin and bone that are grown from the patient cells. This approach is uniquely designed for health studies, 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!