Cellular Special Forces

Find and destroy the tumor

Maxim Russo, Polit.<url>, based on the materials of Science: Reprogrammed skin cells shrink brain tumors in mice.

Scientists from the USA reprogrammed skin cells so that they could fight a brain tumor. The first successful experiment was conducted on laboratory mice. As a result, mouse tumors shrank to 2- 5% of their original size. Although the method has not yet been tested in humans, it may one day give doctors a quick way to develop personalized treatments for aggressive cancers such as glioblastoma, which kills most patients in 12-15 months. In the experiment with mice, the creation of tumor-homing cells took only four days.

Glioblastomas are a type of tumors that are very difficult to remove surgically. The tumor arises from the cells of the neuroglia surrounding the neurons and ensuring their work. Such tumors, as a rule, do not have clear boundaries.

Glioblastoma cells, like other types of tumors, emit a chemical signal that attracts stem cells. Usually, this role is played by specific IGF-1 and SDF-1 proteins, which in a healthy body serve as a signal that attracts stem cells to the sites of damage, so that there they can differentiate into cells of the desired type and replace them. This phenomenon is called "stem cell roaming". In the case of a tumor, stem cells strengthen it with additional tissue.

Since normal stem cells of the patient begin to actively migrate to the area of the tumor, there is a natural thought to make such cells a means of combating glioblastoma. To do this, you need to equip them with the appropriate weapons that kill tumor cells. The genes of proteins associated with the immune response are usually used as such weapons. For example, the gene of Tag7 or IL12 proteins toxic to tumor cells.

Previous studies have tried to use neural stem cells for this purpose, which give rise to neurons and other brain cells. But only a few developments have been brought to the stage of testing on patients, since it is very difficult to obtain neural stem cells. They can be taken directly from the patient, from a donor, or by genetic reprogramming of adult cells. But getting neural stem cells from humans involves surgery, and reprogramming adult cells increases the likelihood of their degeneration into tumor stem cells. The use of donor cells will also pose doctors with the problem of the patient's immune response to the introduction of foreign cells.

Shawn Hingtgen's group from the University of North Carolina was looking for a way to simplify the process of genetic reprogramming cells to fight glioblastoma. Usually, skin cells (fibroblasts) are converted into pluripotent induced stem cells, and then they are differentiated into neural stem cells, which are sent to migrate to the tumor site. Now, according to the researchers, they have managed to turn this process into a one-step process. They described their experiments in the journal Science Translational Medicine (Bagó et al., Tumor-homing cytotoxic human induced neural stem cells for cancer therapy).

Testing on cell cultures in Petri dishes showed that the resulting cells have the ability to homing. They stubbornly strove for glioblastoma cells, covering a distance of 500 microns in 22 hours, and successfully attached themselves to tumor cells.

Reprogrammed stem cells (red) kill tumor cells (green).

In further experiments, Hinchen and his colleagues tested the ability of the resulting cells to deliver a cancer-fighting agent to glioblastoma in mice. Tumors of mice injected with reprogrammed cells decreased in size by 20 to 50 times compared to the control group. The life expectancy of mice who received injections has almost doubled. In some mice, the researchers removed the remnants of the tumor after exposing it to reprogrammed cells and performed additional treatment by injecting new cells into the site of the former tumor. As a result, the number of residual tumors that developed from the surviving cells of the primary tumor decreased by 3.5 times compared to the control group.

However, there are still experiments to determine the ability of the resulting cells to migrate. In the human brain, they have to travel a distance of several millimeters or even centimeters to find and destroy tumor cells. And this is significantly more than the 500 microns that they passed in the experiment.

A number of researchers question the need to reprogram the patient's own cells. For example, stem cell specialist Evan Snyder from the Sanford Burnham Prebys Medical Discovery Institute in San Diego believes that the body's immune response to foreign cells will contribute to the destruction of the tumor.

Now Hinchen's group is conducting experiments on the use of migrating stem cells to destroy already human glioblastoma cells. While they are at the stage of testing in cell cultures.

Portal "Eternal youth" http://vechnayamolodost.ru  02.02.2017