16 October 2019

Pig's heart

In Russia, animals will be bred to grow organs

Maria Nedyuk, Izvestia

Genetically modified animals, in whose bodies organs will be grown for transplantation to humans, will appear in Russia in the coming years. MIPT has signed an agreement with Chinese scientists to participate in a joint project. Animals with human genes will help to get the most suitable material for transplantation. It will not cause rejection due to the immune response, as it will not be perceived by the human body as alien. At the first stage, specialists will reconstruct the pig genome. Similar work is also planned with non–human primates - Javanese macaques. Transgenic animals are also going to be used for preclinical studies of new drugs.

Edit the embryo

Thousands of people need heart, kidney, liver and other vital organs for transplantation, but there is an acute shortage of donor material, which is now taken mainly from a person who has just died. The problem is compounded by the fact that only genetically identical tissues and organs can be transplanted. The material taken from animals will inevitably be recognized as foreign and rejected by immunity. However, the necessary organs can be created artificially in the laboratory by methods of tissue engineering or try to "grow" inside the body of another biological species.

Scientists of the Moscow Institute of Physics and Technology (MIPT) together with colleagues from China are launching a large-scale project to create genetically modified animals for transplantation. Pavel Volchkov, head of the Laboratory of Genomic Engineering, told Izvestia that the corresponding agreement between MIPT and four Chinese organizations was signed in Shanghai during the Third meeting of the Coordination Commission on Innovation Cooperation and the forum "Investments in Innovation". On the Chinese side, the main interest was the company Clonorgan, which is a venture startup. Representatives of the Chengdu Business Incubator, the Institute of Veterinary and Animal Husbandry of the Chinese Academy of Sciences and the Government of Chongqing also signed their signatures.

– Clonorgan company came to us for help in terms of genome editing, – Pavel Volchkov explained. – The staff of our laboratory has already worked out the technology of creating transgenic animals.

We are talking about xenotransplantation – the transplantation of organs, tissues or cells from an organism of one biological species to another. Geneticists need to ensure that tissues and organs grown in an animal can be transferred to the human body and the transplant would not be rejected due to the immune response, was functional and served for a long time.

Humanized animals

In the scientific literature, animals whose organisms consist of genetically heterogeneous cells (that is, taken from different biological species) are called chimeras. As noted in the MIPT, at the moment more than 10 lines of humanized pigs have already been obtained, carrying the necessary modifications in the genome. While they will be used to test new drugs. Methods of therapy of various diseases (including HIV and oncological diseases) can be tested on such animals. For example, to grow a fragment of a human liver from a pig and test on it a cure for cirrhosis that will be suitable for people.

– Despite Winston Churchill's famous statement that pigs look at us as equals, the differences between us as biological species are great, – Pavel Volchkov noted. – It is important for us to avoid an ultrafast rejection reaction during transplantation. In the future, it will be possible to grow an organ consisting of human tissues inside the animal's body. This technology is called blastocyst complimentation (blastocyst is the next stage of embryo formation after the zygote. – "Izvestia"). Moreover, it can be applied in a personalized way: using cells of a specific patient, which will make the risk of rejection minimal.

In addition to editing pig embryos, scientists have also initiated a project with non-human primates, presumably Javanese macaques.

Promising technologies

As scientists explain, the issue of growing organs for transplantation will not be solved so soon, these are the technologies of medicine of the future. However, some individual tissues and parenchymal organs of the human body (liver, spleen, endocrine glands) can be obtained in the next 5-10 years. For example, researchers will be able to help patients with diabetes mellitus if they grow fragments of the pancreas. According to scientists, in the same way it is possible to solve the problem of bone marrow transplantation, which is needed by a huge number of people on Earth, and there is a catastrophic shortage of donor material. To do this, it will be necessary to transplant human hematopoietic stem cells to animals (bone marrow cells, from which erythrocytes, platelets and various types of leukocytes are obtained. – "Izvestia"). They can be formed in whole or in part from cells taken from a particular patient.

Konstantin Krutovsky, a leading researcher at the N.I. Vavilov Institute of General Genetics of the Russian Academy of Sciences, Professor at the University of Göttingen (Germany), is confident that genomic editing is a big step forward, but, like any new technology, it is associated with certain risks.

– It is necessary to approach this with great caution, using the ageless principle of medicine – "do no harm". Not all the side effects of genomic editing have been studied," the scientist stressed. – Therefore, additional research is needed before using this method in practical medicine. In addition, the scientific community, together with sociologists, economists and legislators, should develop ethical principles and laws governing the use of this method, and strictly monitor their compliance.

Anna Kudryavtseva, Head of the Laboratory of Postgenomic Research at the V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, Head of the Genome Research Center, believes that growing human organs inside animals is promising for medicine in the future. However, the MIPT partners raise doubts.

– I am quite wary of cooperation with the Chinese. They have a lot of breakthrough studies, but half of them eventually turn out to be fake," the expert explained. – Therefore, it is necessary to approach such cooperation with a high degree of responsibility.

The project to create transgenic animals for organ cultivation, which also involves the Institute of the Chinese Academy of Sciences, is supported by the government of Chongqing and local institutes of innovative development. From the Russian side, the Advanced Research Fund may be involved, which finances the MIPT laboratories working in the field of regenerative medicine. The Chinese side has already announced investments in the amount of $7 million, and business incubators are ready to invest tens of millions more if the research is successful.

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