13 December 2019

Dangerous Allies

Stem cells can trigger tumor development

Olga Kolentsova, Izvestia

Now stem cells in Russia are allowed to be used for the treatment of certain diseases. The ban on their use was lifted in 2010. However, there are still no sufficient grounds to recognize the introduction of stem cells as absolutely safe. Scientists of the Kurchatov Institute conducted a study on animals and found out that stem cells can stimulate the development of a tumor, and after irradiation transform into tumor cells and cause cancer.

Stimulate the tumor

The use of stem cells (SC) to restore the body is currently an urgent direction in the treatment of certain diseases. However, the full range of side effects of SC has not yet been studied, and some of them may pose a real threat to health. In particular, biologists from the Kurchatov Institute found out that stem cells are able to provoke the growth of tumors.

To find out, scientists conducted the following series of experiments. Researchers inoculated one group of laboratory mice with a breast tumor. Another group was injected subcutaneously with a mixture of tumor cells and pre-irradiated adipose tissue stem cells in small and sublethal doses. For the third group, a mixture of tumor cells and non-irradiated adipose tissue cells was used. The fourth group was injected with simply non-irradiated stem cells from adipose tissue. A week later, the researchers began to analyze the dynamics of the appearance and growth of tumors.

In the first three groups of experimental animals, tumors began to grow. Just a month after the start of the experiment, the tumors in the rodents from the second and third groups were already 5-10 times larger than in the subjects from the first group. And the mice from the last group did not develop spontaneous tumors even six months after the start of the experiment.

– The fact is that during cultivation (a process in which cells are grown in a nutrient medium under controlled conditions – Izvestia) stem cells secrete a wide range of biologically active molecules into the nutrient medium that have various effects on surrounding tissues," explained Alla Rodina, head of the Department of Cell Biology, Immunology and Molecular Medicine at the Kurchatov Institute Research Center. – Among such molecules there are growth factors that stimulate the division of nearby cells.

Therefore, according to the conclusion of Alla Rodina, the introduction of stem cells to the patient is possible only after the complete exclusion of the presence of neoplasms in him.

Source of danger

However, stem cells can also become dangerous during treatment – when irradiating tumors. To understand which of the cells are most susceptible to mutation and which doses are particularly dangerous, researchers from the Kurchatov Institute studied the effect of radiation on stem cells of laboratory animals. Scientists have studied the effect of gamma radiation and neutrons, they are used in medicine for the treatment of malignant tumors.

In this series of experiments, biologists irradiated stem cells taken from the adipose tissue, bone and brain of laboratory mice. Then the level of formation of double-stranded DNA breaks was analyzed. It was essential to study double-strand breaks, since single-stranded ones are able to recover quickly and correctly, that is, to reproduce the original structure of the chain. The appearance of double–stranded ones - with a high probability leads to the appearance of mutations.

It turned out that the number of double-strand breaks under the action of neutron radiation at a dose of 0.5 Gy was twice as high as under the action of gamma quanta. However, it is known that neutron irradiation is generally more damaging, since these particles are heavy and release more energy when passing through the tissues of the body. With an increase in the dose of both types of radiation, the number of DNA breaks increased.

The reaction of different types of stem cells to the same doses of the same type of radiation also differed from each other. According to experiments, the recovery rate of double-strand DNA breaks of bone marrow stem cells is lower than that of adipose tissue and brain stem cells, according to Yulia Semochkina, a junior researcher at the Laboratory of Cell Biology and Molecular Medicine of the Kurchatov Institute. According to the expert, it is too early to draw final conclusions, especially since the experiments were conducted using stem cells of experimental animals, not humans. But the results obtained allowed us to conclude that bone marrow stem cells recover more slowly after irradiation, and they are more likely to have oncogenic mutations.

– Of course, research on the safety of using stem cells for the treatment of various diseases is a very relevant direction, – said Albert Rizvanov, head of the Laboratory of Gene and Cell Technologies at the Institute of Fundamental Medicine and Biology of KFU. – At the same time, the data obtained by scientists around the world on the malignant transformation of stem cells cultured outside the body are often contradictory. Some groups of researchers report mutation of cells into tumor cells, others – that they are not in danger of any oncological transformation.

But in any case, it is very important to understand the fundamental processes that occur when exposed to radiation on stem cells, the expert believes. And therefore, the research of colleagues from the Kurchatov Institute is important both for fundamental science and for practical healthcare.

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