Cell therapy: who invented it and how it works

Cell transplantation is a treatment method in which healthy cells are introduced into the body of a sick person. Once inside, they help repair damaged tissue and stimulate healing processes. This method apply for the treatment of blood diseases and recovery from certain types of cancer. In the future, the list of therapy options is likely to expand: scientists carry out clinical trials to test the effectiveness of cell transplantation for the treatment of cardiovascular problems, Parkinson's disease, diabetes and multiple sclerosis.

How did cell therapy come about?

Experiments with cell transplantation began in the 19th century. Thus, the French physician Charles Brown-Séquard tried to introduce human hormone cells from the testicles of animals, assuming that this will help prolong youth. A British doctor Watson-Williams

had tried save a teenager with severe diabetes mellitus using sheep pancreas cells. This experiment ended unsuccessfully, the boy died three days later. At the beginning of the 20th century, the Swiss Paul Niehans treated patients for cancer by injecting them with sheep embryonic cells. The physician claimed that the method worked, although there is no other evidence for this.

The first truly successful experiments started in the middle of the twentieth century. Scientists came to the idea that donor material for therapy should be taken from people. Suitable for this task stem cells. Under certain conditions, they are able to transform into any other. The first who tried to transplant them to a person was the American Edward Thomas: in 1956, a physician introduced a patient with leukemia, bone marrow taken from his twin brother. Operation was successfully completed. In 1990 Thomas received Nobel Prize for his contribution to the development of cell therapy.

In 1958, Georges Mate tested how this method works if there is no family relationship between the patient and the donor. He transplanted stem cells to five physicists from Yugoslavia who were exposed to radiation. Four of them helped. But after the procedure, some patients experienced exhaustion of the body. Mate suggested that such a reaction is associated with the response of donor cells to recipient cells: they could not take root and destroyed each other. This condition is called GVHD, or graft-versus-host disease.

Now before transplantation to reduce the risk of cell GVHD cleanse from T-lymphocytes. They are just responsible for blocking and destroying foreign elements in the body. It is not yet possible to completely eliminate the reaction, but there are drugs that help reduce the effect of GVHD.

Over the past 60 years, cell therapy has changed significantly. Now cells for transplantation are taken not only from the bone marrow, but also, for example, blood and adipose tissue. And the source of the material can be not only donors, but also the patients themselves.

What is cell therapy

Depending on the source of material for transplantation therapy divide into three types:

• autologous - cells are taken from the patient;
• syngeneic - in an identical twin;
• allogeneic - from the donor.

In theory, there is another option - xenogenic therapy, when cells are taken from animals. Despite the unsuccessful experiences of the past, this idea is still considered promising. Scientists are discussing its use to treat diabetes, liver disease or cystitis. The pig is considered the most suitable donor for a person.

How cell therapy works

After receiving the material, physicians need to prepare to be introduced into the patient's body. To do this, stem cells multiply and perform a series of manipulations on them that help program them for specific tasks and clean them of components that can increase risks transplant rejection.

The cells are then introduced into the body. The methods are different: through veins, tissues, joints, coronary artery, space around the spinal cord. Everything depends on the disease. After transplantation, the cells need to take root. On average, it takes 100 days. During this time, the patient must be in contact with doctors in order to quickly get help in case of complications.

Before using cell therapy, physicians carry out a series of studies, including an ECG, tomography, and a clinical blood test, to make sure that the patient can tolerate such treatment.

What cells can be used for therapy

1. Adult (postnatal) stem cells

These are specialized stem cells that There is in the body of every adult. They can only transform into certain types of cells. Depending on this, they are divided into types:

• hematopoietic are converted into blood cells;
• neural - in the cells of the nervous system;
• mesenchymal - in the cells of cartilaginous, adipose and bone tissues.

The main source of adult stem cells is the bone marrow. But they can also be found in other parts of the body: for example, mesenchymal ones are found in adipose tissue and dental pulp.

2. Embryonic stem cells

These are young pluripotent cells, that is, those that do not have specialization and can turn into any other. Their receive from a blastocyst - an embryo aged 3 to 5 days. To do this, it is grown in laboratories, artificially fertilizing a donor uterus.

This type of cells has great potential, but there are a number of problems with them. It is important to program them correctly and make sure that in the human body they will turn into cells of the required shape. In addition, there is a risk of spontaneous or uneven increase. Now scientists are working on finding effective mechanisms to control the process.

In addition, the cultivation of embryos for the purpose of obtaining stem cells is not considered ethical by everyone. The solution to this problem can be induced pluripotent cells.

3. induced pluripotent stem cells

They are obtained from adult somatic cells (that is, any other than germ cells). The mechanism for working with them was invented by the Japanese scientist Shinya Yamanaka. He explored embryonic cells to find in them the genes that are responsible for pluripotency. It turned out that four genes are responsible for this - Sox2, Oct4, Klf4 and c-Myc. Now they are called "Yamanaka factors".

After the activation of these genes, the cell gradually loses specialization and returns to the embryonic state. Then it can be programmed as you like. For example, it is possible to remake a cell of nervous tissue into a blood cell. And presumably after the reverse introduction, it will be easier for her to take root in the body.

Now induced pluripotent stem cells considered promising material for transplantation, and in the future they can replace embryonic ones.

4. CAR‑T

Stem cells are not the only possible material for therapy. For example, to fight cancer apply modified T-lymphocytes (CAR-T). These are blood cells that are programmed to search for and destroy cancer. T-lymphocytes are taken directly from the patient. Two catheters are inserted into a person's veins. Through the first, blood enters the tube, where it instantly passes through filtration, and then returns to the body through the second catheter. The procedure lasts 2-3 hours.

In the process, a person's calcium levels may decrease. This leads to muscle spasms, numbness and tingling. Therefore, it is better to carry out such a procedure close to the ward in which the person lies. This is done, for example, in the new research complex of cellular technologies in Obninsk. In addition to CAR‑T based therapy, there will engage in bone marrow transplantation and cancer diagnosis. It is also planned to develop four drugs based on somatic cells.