Subverting animal experiments, chip organs for "gradual freezing" test new drugs

<

Organ chip, as an emerging technology developed in recent years, was listed as one of the “Top Ten Emerging Technologies” by the 2016 Davos Forum. It is not a simulator that uses silicon electronic chips for human organ simulation, but contains The biochip of true human living cells, in other words, the organ chip is not to create the entire intact organ of human beings, but to simulate the smallest functional unit in human organs, to realize the interaction of drugs or chemicals in the non-living environment, to study the interaction of living environment, It has important application prospects in the fields of new drug testing, stem cell research, tissue organ development and toxicology prediction.

Among them, drug testing is currently a widely used field of organ chips, and some scientists say that this change in animal testing will be subversive. People have always tried drugs through animals, and it is humane to test drugs regardless of animals. From the perspective of experimental accuracy, although the proportion of genes shared by animals and humans is as high as 99%, the remaining 1% still causes great variables, resulting in huge physiological differences between the two species. The same drug, the response in animals and humans may be quite different. Even small differences in expression will continue to magnify as the drug development process progresses, eventually leading to the failure of the entire project.

Recently, a team at the Massachusetts Institute of Technology (MIT) published a research article in Science Progress, which stated that they used a method of making 3D models of nerve and muscle tissue on microfluidic chips. With this "chip organ", striking differences between healthy neurons and "frozen" neurons were observed, and two new drugs still in clinical testing were tested.

In March of this year, the death of the famous physicist and cosmologist Stephen Hawking, which has been fighting 55 years of amyotrophic lateral sclerosis (ALS), has once again attracted the attention of the world. This disease, commonly known as "gradual freezing disease", is actually a chronic progressive disease that invades the spinal cord, brainstem, and brain motor neurons. The neurons that control muscle movement slowly degenerate and damage because of unclear reasons. And death, the muscles slowly lose their athletic ability until they die. Because these functions gradually lose with the progress of the disease, and the body is gradually frozen, the patient is called a “frozen person” and the average survival time is only 3 to 5 years.

ALS is very rare, and about 4 to 6 out of 100,000 people may suffer from this disease. Among them, the vast majority of patients are ill after adulthood, the cause of the disease is still unknown, and some cases are considered to be related to genetic and genetic defects. Although the incidence rate is very low, ALS poses a great threat to the quality of life and life of patients, and there is currently no clinically effective drug. However, scientists have been studying ways to delay the progression of patients with gradual freezing.

In constant research, scientists have discovered that the junction between motor neurons and muscle cells, the muscle nerve connector, is the key to simulating "frozen disease." For decades, scientists have been limited by the 2D model structure.

In 2016, MIT mechanical and bioengineering professor Roger Kamm team first made a 3D model of the murine muscle nerve connector using microfluidic chip technology. This is a technology that simulates the human body environment in a micrometer-scale chip, integrates basic operation units, and automatically completes the entire process of analysis.

They placed neurons and muscle fibers in two adjacent compartments on the chip. The neurons gradually extend out of the often neurites and eventually connect with the muscle fibers that are wound around the two flexible columns. These neurons have been edited using optogenetic techniques to stimulate muscle contraction under light control. By observing the displacement of the two flexible columns, the researchers can measure the strength of muscle contraction.

In the results of this publication, the Cam team replaced human neurons and muscle cells. Some of these neurons are differentiated from induced pluripotent stem cells (iPSCs) in healthy people, and some are differentiated from induced pluripotent stem cells from patients with sporadic ALS.

The results of the experiment showed that the neurons in the "frozen" group had slower growth neurites and could not establish strong connections with muscle fibers. In addition, the number of neuronal degeneration and muscle cell death is also greater. Two weeks later, ALS motoneurons exerted control on the muscles, only a quarter of healthy neurons.

After demonstrating that "chip organs" can effectively simulate "frozen disease," the Cam team began exploring the ability of the model to test.

The study selected two new drugs, Rapaycin and Bosutinib, which are still in clinical testing. The results of the simulation on the "chip organ" show that both drugs can help the muscles to contract under the stimulation of motor neurons and improve the survival rate of neurons. More importantly, each of the two drugs has a limited ability to penetrate the blood-brain barrier (the barrier between the capillary wall and the plasma and brain cells formed by glial cells), but at the same time it can effectively penetrate the barrier. .

Currently, the Cam team is working with local biotech companies to collect 1,000 “gradually frozen” induced pluripotent stem cells for large-scale drug trials on “chip organs”.

Endotracheal Tube

endotracheal tube,ett tube,tracheal tube,intubation tube

2 MEDS TECHONOLOGY CO.,LTD , https://www.2-meds.com