The invention of the researchers from the Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine (IMBG) started with… the rescue of a child. In 2005, a three-year-old boy received severe burns and surgeons-combustiologists from the capital hospital No 2 appealed to the institute’s researchers with a request to help save the child’s life. It was necessary to restore the base of the skin, the so-called dermis, before autotransplantation. A group of researchers led by Lyubov Lukash immediately prepared wound covering using donor mesenchyme stem cells (MSCs). A covering was applied to the wound surfaces and a few days later the transplantation was carried out. The child recovered.
Since that time, the researchers have been working on the creation and study of dermal wound coverings. With the grant funding from the National Research Foundation of Ukraine, they created a new biotechnological product – derma equivalent, which has no analogues in the world.
We ask the PI of the project ‘Investigation of the therapeutic effectiveness and safety of new dermis equivalents with the inclusion of a composite (the drug isatizion and the cytokine EMAP II) for the treatment of traumatic skin lesions’, the Head of the Department of Human Genetics of the IMBG of the National Academy of Sciences of Ukraine Lyubov Lukash: “What is the essence of the invention?”
The Professor said that the development is based on cellular biotechnology: creation of dermal equivalents with the inclusion of a complex of biologically active substances synthesized by MSCs and a pharmaceutical composite (the isatisone drug in combination with the recombinant EMAP II protein).
Many years of work on the creation of a biotechnology resembles a scientific detective story and can become a plot of a film about important to humanity inventions. As soon as it was possible to solve one problem, another one immediately arose. But the scientists did not give up!
Initially, the doctors asked to shorten the period of recovery of the dermal layer of the skin before performing the autotransplantation. It was worked! Thanks to the application of natural and artificial membranes containing donor stem cells in the composition of medical hydrogels to the surface of burn wounds, the regeneration of the dermis was reduced from seven to two days.
“The doctors were satisfied with the results of the research, the only thing that worried them was the possibility of distant negative consequences after the introduction of foreign donor cells,” the Professor continued telling. “Therefore, they asked to develop dermal coverings without the use of living cells. And we came up with how to do it!
Instead of living cells, scientists began to use nutrient media conditioned by MSCs grown in culture. Experiments on animals have confirmed that cell-free conditioned media (CFCM) are even more effective in healing burn wounds than stem cells. The only complication that sometimes occurred was wound infection.
Therefore, the researchers decided to introduce into the composition of the drug a pharmaceutical composite (the drug isatisone and the cytokine EMAP II) which has antiseptic and immunomodulatory properties. This is how the main task of the project which received grant funding from the NRFU was formulated: to investigate the therapeutic effectiveness and safety of new dermis equivalents with the inclusion of a therapeutic composite.
“During the implementation of the project, we used freeze-dried CFCM powders, which can be stored in a regular refrigerator, while living cells require a special freezer with a temperature of -80o C,” mentioned Lyubov Lukash. “The new drug was tested on model animals, and there were no cases of infection! Toxicological characteristics of the new combined dermal equivalents confirmed their safety.”
Thus, as performing the NRFU project (2020-2021), researchers managed to create a new domestic biotechnological product that is effective, safe and inexpensive compared to foreign analogues.
By the way, a huge achievement of the project is also the new equipment which the institute purchased thanks to the grant funding. This is a CO 2 incubator for developing living cells and a low-temperature refrigerator for long-term storage of samples of cell suspensions, CFCM and other biomaterials.
The project was completed in December 2021. The next step should be the production of a new drug (search for business partners, certification and further clinical trials). But these plans were interrupted by the war.
We asked Professor Lukash what these months of war have been like for her.
“The administration of our institution, headed by Director Mykhailo Tukalo, and a group of employees remained in Kyiv and continued their work,” she answered. “Almost every day I walked to the institute (it’s about forty minutes) to finish the experiments started before the war. I was very worried that the enemy shelling would damage the research equipment…”
Explosions were thundering very close, during one of the attacks several windows of the institute were broken. Fortunately, both new and old equipment survived (by the way, the researchers covered it with their own winter jackets and blankets).
“As of today, almost all employees have returned to Kyiv, and our institute is returning to work according to the usual schedule,” the Professor says proudly. “Researchers who are still abroad help the institute, and we are very grateful for that. We understand that difficult times are ahead. Therefore, we are already looking for additional financial opportunities today, and are hoping for grants and international partnership. It will be difficult, but we must move on, rebuild the economy, continue research. I am sure that Ukraine will win, even if it does not happen as quickly as we all would like it to happen.
Svitlana GALATA