A team of researchers from Columbia University’s Department of engineering and Medical Center reported that they have developed a human physiological model in the form of a multi organ chip. The chip is composed of an engineered human heart, bone, liver and skin, which flows through the blood vessels of circulating immune cells to reproduce interdependent organ functions.
The plug and play multi organ chip created by the researchers is the same size as a microscope slide and can be customized for patients. Since disease progression and response to treatment vary from person to person, this chip will eventually provide personalized treatment for each patient. The study was published in the April 27 issue of the journal Nature biomedical engineering.
Inspired by the human body
Engineering tissue has become a key component of disease modeling and testing drug efficacy and safety in human environment. A major challenge for researchers is how to use a variety of engineered tissues that can communicate physiologically to simulate physical function and systemic diseases, just as they do in the body. However, each engineering organization must be provided with its own environment so that the specific tissue phenotype can be maintained for weeks to months, meeting the requirements of biological and biomedical research. Complicating the challenge is the need to connect tissue modules together to facilitate their physiological communication, which is necessary for modeling systems involving multiple organs.
Inspired by the working principle of the human body, the research team has built a human tissue chip system, in which they connect mature heart, liver, bone and skin tissue modules through circulating blood vessels, so that interdependent organs can be like in the human body. Researchers chose these tissues because they have significantly different embryonic origin, structural and functional characteristics, and are affected by cancer therapeutic drugs.
“Providing communication between tissues while maintaining their individual phenotypes has always been a major challenge,” said Kathy ronaldson bochard, lead author of the study and associate research scientist at Columbia University’s stem cell and tissue engineering laboratory,”Because we focus on using tissue models derived from patients, we have to mature each tissue separately so that it can function in a way that mimics the response of patients. We don’t want to sacrifice this advanced function when connecting multiple tissues. In the body, each organ maintains its own environment and interacts with other organs through the flow of blood vessels carrying circulating cells and bioactive factors. Therefore, we choose Choose to connect tissues through vascular circulation while retaining each individual tissue niche necessary to maintain its biological fidelity, mimicking the way our organs connect in the body.”
The organization module can last more than one month
The research team created tissue modules, each in an optimized environment and separated them from common vascular flow through a selectively permeable endothelial barrier. The individual tissue environment can cross the endothelial barrier and communicate through vascular circulation. The researchers also introduced macrophage producing monocytes into the vascular circulation because they play an important role in guiding tissue response to injury and disease efficacy.
All tissues were derived from the same line of human induced pluripotent stem cells and obtained from a small number of blood samples to prove the ability of individualized and patient specific research. Moreover, in order to prove that the model can be used for long-term research, the team maintained tissues that had grown and matured for 4 to 6 weeks after being connected by vascular perfusion for another 4 weeks.
The researchers also demonstrated how the model can be used to study important diseases in the human environment and to examine the side effects of anticancer drugs. They studied the effects of doxorubicin, a widely used anti-cancer drug, on the heart, liver, bone, skin and vascular system. They showed that the test results summarized the effects reported in clinical studies using the same drugs for cancer treatment.
The model was used to study anticancer drugs
The team also developed a new multi organ chip computing model for mathematical simulation of drug absorption, distribution, metabolism and secretion. The model correctly predicted that adriamycin was metabolized into adriamycin alcohol and diffused into the chip. In the pharmacokinetic and pharmacodynamic research of other drugs in the future, the combination of multi organ chip and calculation method provides an improved basis for preclinical to clinical extrapolation, and improves the drug development process.
Researchers say the new technology can identify some early molecular markers of cardiotoxicity, which is a major factor limiting the widespread use of drugs. Most notably, the multi organ chip accurately predicts cardiotoxicity and cardiomyopathy, which usually requires clinicians to reduce the therapeutic dose of Adriamycin or even stop treatment.
The research team is currently using variants of the chip, all in an individualized patient specific environment. Such as breast cancer metastasis, prostate cancer metastasis, leukemia, the impact of radiation on human tissues, the impact of novel coronavirus on multiple organs, the impact of ischemia on the heart and brain, and the safety and effectiveness of drugs. The research team is also developing a user-friendly standardized chip for academic and clinical laboratories to help make full use of its potential to promote biological and medical research.
“We are excited about the potential of this approach. It is designed to study systemic diseases associated with injury or disease and will enable us to maintain the biological properties and communication of engineered human tissue, one patient at a time, from inflammation to cancer,” the researchers said