Artificial body for experiments
The tunable "body on a chip" model can change the approach to drug development by simultaneously evaluating the effectiveness and toxicity of drugs for both target cells and other organs, such as, for example, the heart or liver. Hesperos Biotech Corporation in Florida, in collaboration with pharmaceutical giant Roche and the University of Central Florida, presented an innovative multi-organ in vitro (outside the body) model system, the data from the use of which are identical to those in vivo (inside the body).
The tunable system of the human body on a chip simulates the interaction of organs with each other and the reaction to drugs. Source: Hesperos Inc.
The therapeutic index is the ratio of the amount of a drug that causes a therapeutic effect to the amount of the same drug that exhibits toxicity. Currently, this index can be determined on animals in the preclinical stage of the study. But the reaction to the drug of animal models does not always coincide with the reaction of the human body. The "body on a chip" system will reliably calculate the therapeutic index for a person, in addition, it will be useful for testing various drugs on tissue models of a particular cancer and obtaining information for each patient. The "body on a chip" system can also be used to select the dose of drugs and will help to abandon the current practice of converting an effective dose for animals into a dose for humans.
The Hesperos group tested the system in two scenarios: on human bone marrow cancer cell lines to evaluate anti-leukemia drugs and on vulvar and breast cancer cell lines to test the effectiveness of a combination of drugs in resistant cancer.
For both configurations, a "body on a chip" system has been developed that can accommodate a variety of human organ-like tissue structures grown on a variety of modules of biological microelectromechanical systems (bio-MEMS) in a single recirculating serum-free environment that allows non-invasive measurements of the response to exposure.
For the leukemia model, two bone marrow components were combined with liver tissue in order to measure the cytostatic properties of two drugs – diclofenac and imatinib – on bone marrow cells and side effects on the liver. Testing showed that liver viability was not affected by imatinib, but was reduced by 30% while taking diclofenac.
In the second experiment, one line of vulvar cancer cells with multidrug resistance and one line of breast cancer cells without multidrug resistance were combined into a system with liver tissue and heart muscle. Tamoxifen reduced the survival rate of breast cancer cells only after transformation in the liver. Tamoxifen had no effect on vulvar cancer cells, except in cases of simultaneous use with verapamil, a calcium channel inhibitor. Both tamoxifen and tamoxifen with verapamil had an effect on the strength and frequency of contraction of the heart muscle, but did not reduce survival.
The results of the experiments corresponded to what was previously reported in human studies, but they were obtained in the laboratory, without the participation of animals and without risk to humans.
It is worth adding that models of many organs can be placed in the "body on a chip": liver, heart, bone marrow, skeletal muscles, neurons of the spinal cord and brain and other tissues, as well as cancerous tumors. The system can be used to evaluate the effectiveness and safety of drugs and their combinations, as well as to create models of various diseases.
Article by C. W. McAleer et al. Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics is published in the journal Science Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Eurekalert: Human-on-a-chip model tests cancer drug efficacy and toxicity for therapeutic index.