04 March 2010

A bioreactor to himself

A person can grow his own organstext: Nadezhda Markina, Infox.ru
The unique technology was brought to Russia by the famous surgeon from Barcelona, Professor Paolo Macchiarini.

He grew the patient a new trachea inside her own body. The professor shared the details of the technology with Russian doctors and a correspondent Infox.ru .

The idea of replacing diseased or worn-out human organs with new ones from the realm of fiction is gradually turning into reality. Specialists pin the same hopes on regenerative technologies in the medicine of the future as on gene therapy. And at the same time, a person is not at all in danger of turning into a cyborg, since body parts will be grown from his own cells.

Regenerative medicine includes both cell therapy, in which damaged human tissue cells are replaced with new ones, and tissue engineering. This is the next step when it becomes possible to replace a tissue or an entire organ.

An example of the fact that such technologies are already possible today is the unique operations performed by Paolo Macchiarini, professor at the University of Barcelona and the Medical School of Hanover, head of the University of Barcelona Clinic.

In 2008, he replaced the patient's trachea, which had lost patency due to tuberculosis, and the woman could hardly breathe. The new trachea was grown on a skeleton obtained from a deceased donor using the patient's own cells.

Fatal stem cellsThe key element of regenerative medicine is stem cells.

These are undifferentiated cells that have not lost their potential for reproduction. Depending on the period of development of the organism, they can turn into cells of any tissue (totipotent cells), into cells of any tissue with some exceptions (pluripotent cells) or into cells of a certain tissue. The first two properties are possessed by embryonic stem cells. But also in the tissues of the adult body there is a certain number of stem cells that divide and replace the cells of these tissues. Thus, the fabrics are constantly updated.

"Actually, tissue regeneration goes back to Prometheus," Paolo Macchiarini noted, "whose liver was constantly pecked by an eagle, but it was restored." Today we understand that stem cells should be thanked for this.

In recent years, scientists have learned to endow pluripotency (the ability to develop into different tissues) stem cells of an adult organism, in particular bone marrow stroma cells. Scientists set the differentiation path for cells by treating them with special proteins — growth factors.

Stages of the first operationFor tissue engineering, an organ frame is needed.

They were served by the trachea from a deceased donor, the frame of which — cartilage rings and ligaments — was thoroughly cleaned of cells using an enzyme solution.

Bone marrow cells after removal from the patient must be multiplied and differentiated. Their number had to be increased from 30 thousand to about 80 million. A special treatment directed differentiation in the right direction, so that the cells of the bone marrow stroma formed chondrocytes — cells of cartilage tissue — and cells of the ciliated epithelium.

The frame of the trachea with retrained cells was placed in a bioreactor in which the cells formed tissue on its surface. In this form, the animated donor trachea, having cut out a fragment suitable in shape from it, was placed in the patient's body after the removal of the affected area.

Paolo Macchiarini financed all the work out of his own pocket. And the work was not only difficult — its different stages had to be carried out in different places.

"In Barcelona, we isolated cells from the patient's bone marrow and made a matrix," Professor Macchiarini told reporters at a scientific cafe organized by Chemistry and Life magazine with the support of the Dynasty Foundation. — In Bristol, where the best specialists in cartilage and respiratory tissue cells cultured cells. The cell culture was refused to be transported by a regular flight, since the volume of the culture fluid exceeded 100 ml, we had to hire a private plane. The bioreactor was created in Milan. And finally it all came together in Barcelona, where we performed the transplant."

Man is the best bioreactor"After evaluating what has been done, I thought about how to simplify this technology, because in this form it is no longer acceptable today," Macchiarini said.

- And there was an idea that it is possible to grow a trachea not outside, but inside the patient's body."

It was using this technology that, a year and a half later, he performed a second tracheal replacement operation. The frame for it was taken, as before, from a deceased donor, and also cleaned of cells. Bone marrow cells and epithelial cells were extracted from the patient's sinuses, but they were no longer cultured, but directly applied to the skeleton. He was treated with the necessary growth factors. And added erythropoietin.

"We discovered that human fibroblasts have receptors for erythropoietin on their surface,— says Macchiarini. — They are activated when tissue is damaged. Erythropoietin awakens the stem cells sleeping in the body and encourages them to divide."

In this form, the graft was implanted in the patient, and all the other stages took place in her body. It worked like a bioreactor. The cells multiplied, differentiated, and stem cells of the body stimulated by erythropoietin were added to them. As a result, tissues have formed on the trachea, and exactly where it is needed. According to Macchiarini, "stem cells are smarter than us: they themselves know where they need to move." So, the cells of the ciliated epithelium from the outside migrated into the trachea, since there is more oxygen content inside.

Two months after the operation, the transplanted trachea became fully viable. She created her own blood supply system and performed her functions normally.

In a conversation with a correspondent Infox.ru the professor noted that this technology, like all the others, is by no means a panacea. When Infox.ru asked about the possibilities of regenerative medicine regarding the nervous tissue, Macchiarini replied with a sigh: "You have probably touched the Achilles heel of regenerative medicine. We can do something both with nerve damage and with an underdeveloped nervous system. However, it is not yet possible to achieve full recovery. We can restore, for example, motor functions, support, but not tactile sensations. That is, to lay highways, but not the entire road network."

Paolo Macchiarini did not patent his technology. He brought her to our country for free and held a master class for doctors and specialists at the I. M. Sechenov Moscow Medical Academy. I would like to hope that it is not in vain.

And about the achievements of Russian scientists in the field of cellular and tissue regenerative medicine Infox.ru he will tell you in the near future.

Portal "Eternal youth" http://vechnayamolodost.ru04.03.2010

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