Tablet instead of mice
Scientists from Columbia University, led by Tal Danino, have created a platform that simulates a cancerous tumor, which allows you to determine the best method of therapy for each specific case. The use of laboratory animals for the selection of personal therapy is almost impossible due to the duration, complexity and high cost of such studies.
To prove the concept, they focused on testing genetically modified antitumor bacteria that can deliver drugs to inflammatory foci using tumor spheroids. The speed and high throughput of their technology, which is called BSCC (bacteria spheroids co-culture) and ensures the stable growth of bacteria inside tumor spheroids, which makes it possible to conduct long-term studies. The method can also be used for other types of bacteria and cell types. Scientists claim that this is the first study of rapid screening and analysis of bacteria in vitro.
By combining automation and robotics, BSCC helps to test a large number of treatments to discover the most effective. For example, personalize medical procedures by simulating a patient's cancerous tumor in a tablet to quickly determine the best therapy for a particular person.
Many bacteria can grow inside the tumor due to reduced immunity, but outside of it, the body's immune system is active and able to kill bacteria. Inspired by this mechanism, the scientists were looking for an antibacterial agent that could simulate the "killing" of bacteria outside the spheroids. The developed protocol uses the antibiotic gentamicin. Using BSCC, the scientists tested a wide range of programmable anti-cancer bacterial treatment methods. Three-dimensional multicellular spheroids were used because they repeat the conditions of the human body. In addition, the three-dimensional spheroid provides bacteria with enough space to colonize it.
The video shows how bacteria (colored green) "eat" the tumor organoid in a week.
The BSCC system made it possible to quickly characterize colonies of genetically modified bacteria, and then select the best candidate for treatment. A potent colon cancer therapy using bacterial theta toxin was discovered, combined with an optimal genetic map of drug delivery using weakened Salmonella typhimurium bacteria. Combinations of bacterial therapies have also been found that can increase their anti-cancer effectiveness.
The researchers compared their BSCC results with those obtained in animal testing and found similar bacterial behavior. They also found that theta toxin is more effective than the therapy created in the past.
Scientists hope to expand the BSCC to test the possibility of bacterial therapy for various diseases, including gastrointestinal diseases and infections. Their ultimate goal is to use new bacterial treatments in clinics around the world.
Article by Harimoto et al. Rapid screening of engineered microbial therapies in a 3D multicellular model is published in PNAS.
Elena Panasyuk, portal "Eternal youth" http://vechnayamolodost.ru / based on materials
Columbia Engineering: Bacterial Therapy in a Dish.