16 April 2014

Bioengineered esophaguses have been tested on rats

An important esophagus for Russia
A Russian researcher took part in the creation of the world's first
Bioengineered esophagus – article in Nature CommunicationsNadezhda Markina, "Newspaper.

Ru»A Russian researcher participated in the creation and testing of the world's first bioengineered esophagus on rats.

The head of the work, Paolo Macchiarini, spoke about this work "Газете.Ru ".

The research group of Professor Paolo Macchiarini at the Karolinska Institute in Sweden has published in the journal Nature Communications the results of work on the creation of a tissue-engineered esophagus (Sjoqvist et al., Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats). Scientists implanted the constructed organ into rats and made sure that the esophagus retains its functional properties in the body.

Alexander Sotnichenko, a 26-year-old Russian researcher, a post-graduate student from the Kuban State Medical University (Krasnodar), who was an intern at the Karolinska Institute as part of a megagrant of the Government of the Russian Federation, took part in the work. He was one of the first Russian scientists to co-author a publication in the journal of the Nature family in the field of regenerative medicine.


Paolo Macchiarini and Alexander Sotnichenko. Photograph: Science for Life Extension Foundation

This work is an important step towards the creation of a bioengineered esophagus for human transplantation. Such transplantation is needed by patients who have to resect the esophagus due to a cancerous tumor, the consequences of injuries or congenital pathologies of the digestive tract. For example, esophageal cancer is diagnosed in 500 thousand people annually. This is a serious operation associated with a risk to life, and patients who have undergone it can develop serious consequences, in particular, weight decreases sharply. Transplantation could seriously improve the quality of life of these people.

At the first stage of the experiment, the researchers removed all the cells from the rat's esophagus. Thus, they obtained a decellularized biocompatible framework that does not contain genetic material capable of causing organ rejection, but retains the mechanical and bioactive properties of the "living" esophagus. Paolo Macchiarini and his colleagues have already had the experience of obtaining a decellularized tracheal skeleton, which was used for transplantation of bioengineered trachea to patients. For the esophagus, the technique was slightly modified.

Then the scientists seeded the skeleton with cells of the stroma, or mesenchyme, of the rat bone marrow. The experimental animal had a part of its own esophagus removed, making up 20% of its total length. This part was replaced with a bioengineered design.

Ten rats underwent such an operation, and after transplantation, the researchers monitored their condition for two weeks. They made sure that the animals recovered quickly and did not suffer from pain or deterioration. There were no signs of rejection and adverse immunological reactions to the transplant.

Moreover, in the bioengineered esophagus, scientists found several newly formed blood vessels and muscle fibers. After the operation, the animals were fed liquid and soft food. As a result, they gained significantly more weight compared to the control group of rats who underwent a false operation.

The authors warn that the bioengineered graft replaced only 20% of the length of the esophagus in rats and this option may not be in demand in the clinic. In addition, the functional properties of the graft in the long term have yet to be studied.

The researchers plan to carry out a complete replacement of the esophagus in large animals and a longer postoperative follow–up.

Now Alexander Sotnichenko has already returned to Krasnodar, to the International Research Center for Regenerative Medicine created within the framework of the megagrant. He works in a research project to create a tissue-engineered heart. At the moment, experiments are being conducted on rats, but in the near future the group intends to start research on primates.

The head of the study, Professor Paolo Macchiarini, told the newspaper about this work.Ru" at the III International Conference "Genetics of Aging and Longevity" in Sochi:

 "One of the tasks of the megagrant was to train young Russian researchers from the Kuban Medical University at the Karolinska Institute, where they came to study regenerative medicine. Each of them was involved in a project. Alexander participated in a project on the esophagus, another graduate student, Elena Gubareva, was involved in a completely new project to create a bioengineered diaphragm, Elena Kuevda was engaged in bioengineered lungs. Then they returned to Krasnodar and continued to develop these research projects. I want to emphasize that it is very difficult for young researchers to work in another country, not from Moscow and St. Petersburg, but from small cities.

Alexander Sotnichenko was involved in a bioengineered esophagus project, and I am very proud of him. I must say that this project is very important for Russia, because there is a high incidence of esophageal diseases among Russians and in a certain percentage they lead to death. They are relevant not only for adults, but also for children, because there are hereditary diseases of the esophagus, such as fistula or its complete absence.

For the first time in the world, we performed transplantation of a bioengineered esophagus to rats. At the same time, we were convinced that the animals survived and recovered and that the esophagus worked for a long time – 14 days. This is the maximum period during which we could conduct an experiment within the framework of an ethical permit in Sweden. We hope that if we receive the additional funding we are looking for for this project, we will be able to do the same on primates, already in Krasnodar, before conducting clinical transplantation to patients."

"In the field of regenerative medicine, we can and should already move from laboratory research to clinical practice in order to save lives," Paolo Macchiarini said at a conference in Sochi.

Portal "Eternal youth" http://vechnayamolodost.ru16.04.2014

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